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EHS Newsletter
 
Volume 3 Issue 3-4
EHS Newsletter

 

E.H.S. EXECUTIVE BOARD: 

President : M. M. Ibrahim, MD
Vice President : H. E. Attia, MD
Secretary : H. Rizk, MD
Treasurer : W. El Aroussy, MD
Members :
A. M. Hassaballa, MD
M. S. Mokhtar, MD
S. EI-Tobgy, MD
O. Khashaab, MD
M. M Gomaa, MD

 

EDITORAL COMMITTEE:

 

Editor : M. Hamed, MD
Assistant Editors :
A.M. EI-Keiy, MD
A. EI-Etriby, MD
M. El Ramly, MD
H. Gobran, MD
W. El Naggar, MD
Z. Ashour, MD

 

PRESIDENT'S MESSAGE:

CURRENT TRENDS IN PATHOPHYSIOLOGY OF HYPERTENSION

The basic hemodynamic abnormality in the majority of patients with essential hypertension is an increase in systemic arterial resistance. Vasoconstriction and hypertrophy of resistance arterioles will decrease the lumenal cross sectional area and the lumen to wall ratio. Vasoconstriction and hypertrophy result from disordered regulation of a number of control systems in the hypertensive patients which include neurogenic, humoral and molecular.

Neurogenic dysregulation occurs secondary to disturbances in baroreflex control pathways, suprasegmental or peripheral neurogenic dystunction. The final outcome of the disordered neurogenic regulation is an increase in sympathetic nervous activity. There are evidences of sympathetic nervous system overactivity in a subset of hypertensive patients. In early hypertension there is increased plasma norepineplirine (NE) and vascular reactivity to NE.

Direct microneurographic recordings of peroneal and tibial nerves showed increased muscle sympathetic nerve activity. Disordered humoral regulation in hypertension results in an imbalance between vasoconstrictor and vasodilator hormones favoring vasoconstriction. Increased activity of a number of pressor hormones and decreased vasodilators production was demonstrated in hypertensive patients or individuals genetically predisposed to hypertension.

Vasoconstrictor hormones include angiotensin 11, NE, endothelin, arginine, vasopressin. insulin, vasopressor prostaglandins and circulating endogenous Quabian-like substance. Vasodilator hormones include the Kallikrein-kinin system, natriuretic peptides, nitric oxide, prostacyclins, medullipin, calcitonin-gene-related peptide and adrenomedullin. Plasma levels of these vasoactive substances may not reflect their actual state of production since many of them act as local hormones and produce their effects through paracrine and autocrine mechanisms.

Furthermore, the circulating plasma levels of these hormones is determined beside their rate of production by other factors such as the rate of clearance, enzymatic degradation, receptor sensitivity, feed back systems and transient responses to physiologic stimuli. Clinical evidences of humoral abnormalities are present in a number of conditions.

Increased plasma levels of angiotensinogen were present in individuals genetically predisposed to hypertension and there was a genetic linkage between angiotensinogen gene and hypertension. Failure to modulate A-l 1 levels is present in a subset of hypertensive patients. Increased endothelin levels are present in prceclampsia. High fasting plasma insulin levels could predict development of hypertension and there was a positive association between insulin and blood pressure in certain races.

Elevated plasma arginine vasopressin was reported in 30% of male hypertensives. Increased circulating endogenous quabain like substance was described in essential hypertension and primary' aldosteronism. On the other hand the urinary Kallikreins are decreased in children of hypertensive parents. There are evidences of impairment in endothelium dependant vasodilation and nitric oxide dependant vasodilatory responses in hypertension.

Decreased excretion of prostacyclin metabolites may occur in some hypertensives. Disordered regulation at the molecular level include abnormalities in cell membrane transport systems, sigual transduction pathways and genetic defects. Increased intracellular cytosolic Ca++ was reported in hypertensive patients and was found to correlate in some studies with the level of arterial pressure.

Mechanisms responsible for increased cytosolic Ca++ include augmented activity of voltage operated Ca+t channels (LAype) favoring intrusion of Ca++ inside the cell. Iriliibition of Ca++ pumps and Na' - Ca++ exchanges will decrease the extrusion of Ca++ outside the cell.

Cytosolic Cat+ is a major intracellular sigual transduction molecule (secondry messenger) mediating a host of cellular activities which include activation of myosin-light chain kinase and myofibrillar shortening and contraction, Increased intracellular sodium was also reported in hypertensive patients due to impairment in Na/K pump and Na-K-Cl co-transport systems beside increased activity of Nat leak channels. All these mechanisms favour increased intracellular Nat .

The Nat - H+ exchange system is augmented in hypertension leading in addition to increased Nat to a reduction in H+ and increase in intracellular pH.

Vascular smooth cell hypertrophy is present in hypertensive patients, although evidence suggest that it is a secondary process, there is a possibility that this might occur as an initial event. Increased activity of a large number of growth promoting factors can produce vascular hypertrophy.

Growth promoters include in addition to vasopressor vasoactive substances a number of growth factors and cytokines such as PDGF, FGF, EDGF, IL-GF, IL 1, etc. A number of genetic abnormalities were reported in hypertensive patients. These include polymorphism of ACE gene and insulin receptor gene. Abnormality of angiotensinogen gene produces variant molecular form of angiotensinogen and elevated plasma angiotensinogen. Abnormalities can occur in I 1-B hydroxylase gene resulting in a syndrome of glucoid suppressed hyperaldosteronism. Other gene abnormalities related to development of hypertension include genes coding for Na; K ATPase enzyme, Kallikrein, ANP, Dopamine - B hydroxylase and Ns+-K+ co4ransport.

CONCLUSION:

Regulation of vascular tone and growth and sytemic vascular resistance is under coistrol of a complicated system of regulatory mechassisms which include sympathetic nervous system and a large number of vasopressor, vasodilator and growth promoting hormones acting through endocrine paracrine and autocrine mechanisms to influence vascular smooth muscle cell activity.

A defect at the molecular level in cell membrane transport systems and in the genes can explain some of the cellular ionic and metabolic abnormalities in hypertensives which lead to an increase in systemic vascular resistance.

M. Mohsen Ibrahim, MD
Professor and Chairman of the Cardidogy
Department-Cairo University.
Prineipal Investigator the Egyptian National Hynertension Project

 

Editorial

E.H.S. EXECUTIVE BOARD: 

President : M. M. Ibrahim, MD
Vice President : H. E. Attia, MD
Secretary : H. Rizk, MD
Treasurer : W. El Aroussy, MD
Members :
A. M. Hassaballa, MD
M. S. Mokhtar, MD
S. EI-Tobgy, MD
O. Khashaab, MD
M. M Gomaa, MD

 

EDITORAL COMMITTEE:

 

Editor : M. Hamed, MD
Assistant Editors :
A.M. EI-Keiy, MD
A. EI-Etriby, MD
M. El Ramly, MD
H. Gobran, MD
W. El Naggar, MD
Z. Ashour, MD

 

PRESIDENT'S MESSAGE:

CURRENT TRENDS IN PATHOPHYSIOLOGY OF HYPERTENSION

The basic hemodynamic abnormality in the majority of patients with essential hypertension is an increase in systemic arterial resistance. Vasoconstriction and hypertrophy of resistance arterioles will decrease the lumenal cross sectional area and the lumen to wall ratio. Vasoconstriction and hypertrophy result from disordered regulation of a number of control systems in the hypertensive patients which include neurogenic, humoral and molecular.

Neurogenic dysregulation occurs secondary to disturbances in baroreflex control pathways, suprasegmental or peripheral neurogenic dystunction. The final outcome of the disordered neurogenic regulation is an increase in sympathetic nervous activity. There are evidences of sympathetic nervous system overactivity in a subset of hypertensive patients. In early hypertension there is increased plasma norepineplirine (NE) and vascular reactivity to NE.

Direct microneurographic recordings of peroneal and tibial nerves showed increased muscle sympathetic nerve activity. Disordered humoral regulation in hypertension results in an imbalance between vasoconstrictor and vasodilator hormones favoring vasoconstriction. Increased activity of a number of pressor hormones and decreased vasodilators production was demonstrated in hypertensive patients or individuals genetically predisposed to hypertension.

Vasoconstrictor hormones include angiotensin 11, NE, endothelin, arginine, vasopressin. insulin, vasopressor prostaglandins and circulating endogenous Quabian-like substance. Vasodilator hormones include the Kallikrein-kinin system, natriuretic peptides, nitric oxide, prostacyclins, medullipin, calcitonin-gene-related peptide and adrenomedullin. Plasma levels of these vasoactive substances may not reflect their actual state of production since many of them act as local hormones and produce their effects through paracrine and autocrine mechanisms.

Furthermore, the circulating plasma levels of these hormones is determined beside their rate of production by other factors such as the rate of clearance, enzymatic degradation, receptor sensitivity, feed back systems and transient responses to physiologic stimuli. Clinical evidences of humoral abnormalities are present in a number of conditions.

Increased plasma levels of angiotensinogen were present in individuals genetically predisposed to hypertension and there was a genetic linkage between angiotensinogen gene and hypertension. Failure to modulate A-l 1 levels is present in a subset of hypertensive patients. Increased endothelin levels are present in prceclampsia. High fasting plasma insulin levels could predict development of hypertension and there was a positive association between insulin and blood pressure in certain races.

Elevated plasma arginine vasopressin was reported in 30% of male hypertensives. Increased circulating endogenous quabain like substance was described in essential hypertension and primary' aldosteronism. On the other hand the urinary Kallikreins are decreased in children of hypertensive parents. There are evidences of impairment in endothelium dependant vasodilation and nitric oxide dependant vasodilatory responses in hypertension.

Decreased excretion of prostacyclin metabolites may occur in some hypertensives. Disordered regulation at the molecular level include abnormalities in cell membrane transport systems, sigual transduction pathways and genetic defects. Increased intracellular cytosolic Ca++ was reported in hypertensive patients and was found to correlate in some studies with the level of arterial pressure.

Mechanisms responsible for increased cytosolic Ca++ include augmented activity of voltage operated Ca+t channels (LAype) favoring intrusion of Ca++ inside the cell. Iriliibition of Ca++ pumps and Na' - Ca++ exchanges will decrease the extrusion of Ca++ outside the cell.

Cytosolic Cat+ is a major intracellular sigual transduction molecule (secondry messenger) mediating a host of cellular activities which include activation of myosin-light chain kinase and myofibrillar shortening and contraction, Increased intracellular sodium was also reported in hypertensive patients due to impairment in Na/K pump and Na-K-Cl co-transport systems beside increased activity of Nat leak channels. All these mechanisms favour increased intracellular Nat .

The Nat - H+ exchange system is augmented in hypertension leading in addition to increased Nat to a reduction in H+ and increase in intracellular pH.

Vascular smooth cell hypertrophy is present in hypertensive patients, although evidence suggest that it is a secondary process, there is a possibility that this might occur as an initial event. Increased activity of a large number of growth promoting factors can produce vascular hypertrophy.

Growth promoters include in addition to vasopressor vasoactive substances a number of growth factors and cytokines such as PDGF, FGF, EDGF, IL-GF, IL 1, etc. A number of genetic abnormalities were reported in hypertensive patients. These include polymorphism of ACE gene and insulin receptor gene. Abnormality of angiotensinogen gene produces variant molecular form of angiotensinogen and elevated plasma angiotensinogen. Abnormalities can occur in I 1-B hydroxylase gene resulting in a syndrome of glucoid suppressed hyperaldosteronism. Other gene abnormalities related to development of hypertension include genes coding for Na; K ATPase enzyme, Kallikrein, ANP, Dopamine - B hydroxylase and Ns+-K+ co4ransport.

CONCLUSION:

Regulation of vascular tone and growth and sytemic vascular resistance is under coistrol of a complicated system of regulatory mechassisms which include sympathetic nervous system and a large number of vasopressor, vasodilator and growth promoting hormones acting through endocrine paracrine and autocrine mechanisms to influence vascular smooth muscle cell activity.

A defect at the molecular level in cell membrane transport systems and in the genes can explain some of the cellular ionic and metabolic abnormalities in hypertensives which lead to an increase in systemic vascular resistance.

M. Mohsen Ibrahim, MD
Professor and Chairman of the Cardidogy
Department-Cairo University.
Prineipal Investigator the Egyptian National Hynertension Project

 

Abstracts of World Literature
Insulin-like growth factor binding proteins in arterial
hypertension: relationship
to left Ventricular
hypertrophy.
Diez J; Laviades C; Martinez E; Gil MJ; Monreal I;
Fernandez J; Prieto J
Department of Internal Medicine' University of
Navarra' Pamplona' Spain.

OBJECTIVE: it was reported previously that circulating insulin-like growth factor I levels are abnormally elevated in patients with essential hypertension and left ventricular hypertrophy. Tissue availability of the factor depends on the distribution of the circulating hound factor between its high-and low molecular mass binding proteins' only the latter being able to cross the endothelium. The aim of this study was to investigate whether the presence of the different serum binding proteins is altered in-patients with essential hypertension and left ventricular hypertrophy.

DESIGN: The study was performed in 30 never-treated patients with essential hypertension and 30 age and sex-matched normotensive subjects. Patients were separated into two groups according to the presence or the absence of echocardiographically determined left ventricular hypertrophy.

METHODS: Plasma insulin-like growth factor I levels was determined by specific radioimmunoassay. The different molecular forms of its serum binding proteins were analyzed by Western blotting using [l25I -labeled insulin-like growth factor]. A densitometric scanning of the blots was performed to analyze the quantitative relationships between the different forms of binding proteins.

RESULTS: Insulin-like growth factors I level were significantly higher in the hypertensive patients with than in the hypertensive patients without left ventricular hypertrophy or in the normotensive subjects. Compared with the normotensive subjects' both hypertensive patients subgroups exhibited increased high-molecular mass binding protein type 3 and decreased low-molecular mass binding proteins types 1 and 2. However' changes in the binding proteins were more marked in the hypertensive patients without than in the hypertensive pwith left ventricular hypertrophy. Accordingly' the ratio of low- to high-molecular mass binding proteins (an index of insulin-like growth factor I bioavailability) was higher in the hypertensive patients with than in the hypertensive patients without left ventricular hypertrophy.

CONCLUSIONS: These results show that the distribution of the molecular forms of serum insulin-like growth factor binding proteins is altered in patients with essential hypertension' independently of insulin-like growth factor 1 levels This suggests that regulation of the binding proteins is abnormal in essential hypertension. Whether the tissue availability of circulating insulin-like growth factor I is higher in hypertensive patients with than in hypertensive patients without left ventricular hypertrophy merits further investigation.

J Hypertens, 13:349-55, 1995 Mar

Factors influencing LVM in hypertensive type-I
diabetic patients.
Gerdts E; Myking OL; Lund-Johansen P; Omvik P
Department of Heart Disease' Haukeland Hospital'
Bergen' Norway.

Diabetes mellitus is associated with a high prevalence of hypertension and left ventricular hypertrophy (LVH)' and a causative relationship with abnormal sodium metabolism in diabetic patients has been suggested. Factors influencing left ventricular mass (LVM) were assessed in 30 hypertensive type- 1 diabetic patients' mean age 46 +/- 9 (range 24-67) years with a mean duration of diabetes and hypertension of 19 +/- 10 and 6 +/- 5 years' respectively. In the total study population' casual blood pressure was 163/94 +/- 24/10 mmHg and 24 h blood pressure was 155187 +/-17/8 mmHg. Twenty-four-hour urine samples were obtained to measure daily albumin excretion (0.77 +/- 1.06 g) and dietary sodium intake was assessed as 24 h sodium excretion (173 +/-77 rnmol). Creatinine clearance averaged 1.41 +/- 0.53 ml/s. LVM determined by echocardiography was 221 +/- 74 g (range 104-408 g) and 33% of the patients had LVH. Multiple regression analysis identified dietary sodium intake and plasma atrial natriuretic peptide as independent predictors of LVM (R2 = 0.52' p <0.00l). No significant association was found between LVM and blood pressure or albuminuria. The results propose dietary sodium intake as an important factor in the development of LVH in hypertensive type-I diabetic patients.

Blood Press, 6:197-202, 1997 Jul

 

Abstracts of Local Literature
Plasma level of endothelin 1, insulin and catecholamines are
not increased in patients with essential HTN and no target
organ damage

Insulin resistance and reactive hyperinsulinaemia commonly occur in-patients with essential hypertension (EHT). However, the link between vascular and metabolic disturbances is still unclear. Endothelin l(ET- 1) is a very potent vasoconstrictor peptide whose role in hypertension is still controversial. Recently, the possibility that hyperinsulinaemia may potentiate ET- 1 gene expressiona nd its receptor mediated action amy be relevant to the role of hyperinsulinaemia in the pathogenesis of cardiovascular diseases. Multiple experimental evidences point to an interaction between ET- 1 and catecholamines (catechols) suggesting that sympathetic activity may be modulated by ET- 1. The aim of the work was to study the plasma levels of these hormones in mild versus severe hypertensive pts and the relation of these hormones to BP levels in these patients.

Forty patients with EHT and no target organ damage were studied. They were not diabetic, not obese and not on antihypertensive treatment for the last 2 weeks. They were assigned to either of 2 groups according to blood pressure (BP) level: Gr A included 20 pts with mild EHT (BP> 14(3)190 and < 160/100). mean age was 52+8 years. Grp B included 20 patients with severe EHT (BP> 1801110). mean age was 52.8 + 9 years. Twenty normotensive volunteers served as controls (C). mean age was 49.6 years. Plasma levels of ET--1 and insulin were measured by specific radioimmuno assay and catechols by high performance liquid chromatography. Molar insulin/glucose ratio (I/G) was calculated in the fasting state and 1h and 2h after an oral glucose load of 75 gm

Results:

  C Gr A Gr B
F.ET-l

(pg/ml)

0.36 +

 

0.19

0.5 +

 

0.23

0.39 +

 

0.17

F.Catechols (nmol/ml) 2.23 +

 

1.03

3.68 +

 

2.47

3.4 +

 

2.69

F.Insulin

 

(u/ml)

8.9 +

 

2.4

8.7 +

 

2.3

9 +

 

1.8

I/G -2h 44.2 +

 

24.7

32.6 +

 

18.7

56.4 +

 

41.3 *

P < 0.05 Vs Gr A

No significant difference was found between the 3 groups as regards the plasma levels of these hormones. It was only the I/C ratio 2 hours after an oral glucose load which differed significantly between Gr B and Cr A.. No significant correlation was found between plasma levels of studied hormones and systolic, diastolic and mean BP in the same patients.

In conclusion, plasma levels of ET- I, catechols and insulin are not related to B levelsin pts with EHT and no target organ damage. Severe hypertension is associated with increasing insulin resistance, which is also unrelated to BP level. The fact that ET-l is mainly an autocrine/paracrine hormone and its circulating level does not reflect the local concentration of the peptide in the vessel wall may explain the lack of correlation between plasma levels of studied hormones as well as the lack of their correlation with the magnitude of BP.

Abstract presented in the 2nd meeting of the Egyptian Hypertension Society 1996.

Extent and functional capacity of coronary collateral
circulation in hypertensive patients with
atherosclerotic coronary disease
Aly M. Hegazy, M.D. and Aly Ramzy, M,D.

The aim of this study was the evaluation of coronary collateral circulation in relation to the presence of systemic hypertension and left ventricular hypertrophy. One hundred patients with significant coronary artery disease (>75%) were enrolled in the study. Thirty-five hypertensive patients with left ventricular hypertrophy (LVH) were considered as group I, 35 hypertensive patients without LVH as group II and 30 normotensive patients as group III. Coronary angiography was done for all patients. Class 0: no collaterals, class I: partial filling and class II: complete filling of collaterals were used as angiographically classified coronary collaterals. Echocardiography and graded exercise ECG test were done for all patients. There was a non-significant difference between hypertensive and normotensive patients as regards clinical characteristics. There was a significantly increased number of patients with class II collaterals (p <0.01) among hypertensive patients compared to normotensive patients. There was a non-significant difference between the 3 groups of the study as regards coronary artery disease and stenosis, but there were significantly more proximal lesions in patients with class II collaterals (p<0.0 1) and increases distal lesions in patients without collaterals (p<0.01). There was a significant increase in coronary perfusion pressure (p<0.0 1) in patients with class I and II collaterals. There was a non significant difference between the patients of the 3 study classes as regards the systolic function of the left ventricle and segmental wall motion abnormalities, but there was significantly increased left ventricular mass (LYM) and LVM index (p<0.0l) in the patients of class II than those of class I and class 0. There was a non-significant difference in functional capacity inpatients of class II, I and 0 as there was a non significant difference between the 3 classes of the study as regards the Canadian functional classification, exercise tolerance and ST segment depression.

We concluded that patients with systemic hypertension and coronary artery disease have an increase in coronary collateral circulation corresponding to the left ventricular hypertrophy and that the functional capacity of coronary collateral circulation is not augmented by left ventricular hypertrophy.

Abstract presented in the 2nd meeting of the Egyptian Hypertension Society, 1996

CARDIAC CYTOPROTECIVE PROFILE OF SOME
ANTI-HYPERTENSIVES IN RATS A CORRELATION
OF THEIR CARDIAC ANTIOXIDANT-BUFFERING
CAPAClTY TO THEIR RELATED RESPIRATORY
ENZYMES.
Nayel O*, and Youssif M** * Pharmacology & Drug
Toxicology Departme, Faculty of Medicine, **
Histochemistry & Cell Biology Department, Medical
Research Institute, Alexandria University.

Cardioprotection, vasculoprotection and the possession of inherent antioxidant buffering capacity are recent requisites to be fulfilled in an idea antihypertensive agent. No wonder, the objectives of this study focused on questioning the impact of some available antihypertensives, on cardiac respiratory enzymes, probing in their possible correlative ability to modulate the cardiac antioxidant buffering capacity particularly when binge subjected to peroxidative stress [Hypercholesterolaemia being taken as a model].

The 60 male albino rats experimented comprised; 10 normal controls (N) receiving 2% gum acacia daily, 10 oxidatively stressed gp. (S) receiving atherogenic diet, 40 rats oxidatively stressed while continuously receiving either; Amlodipine 5mg/kg/day (S+A)(n=10), or Isradipine 2mg/kg/day (S+I)(n=10), or Captopril 35mg/kg/day (S+c)(n=l0) or fosinopril 8 mg/kg/day. (S+F)(n=10) for 2 months.

Result revealed that (S) suppressed cardiac cytochrome oxidase, succinic dehydrogenase, ATPase and increased lactate dehydrogenase enzyme activities compared to (N), as assessed hi stochemically. It meanwhile Significantly depleted cardiac enzymatic antioxidant buffering capacity as judged by SOD and catalase activities and significantly increased lipid peroxidation as indexed by MDA seruin levels that were assessed biochemically. On the other hand. The studied antihypertensives variably conferred cardioprotection, where S+I>S+A and S+C>S+F succeeded to revert all cardiac enzymes assessed histocheinically toward (N) as compared to (S)

They also significantly variably elevated cardiac antioxidant buffering capacity and decreased lipid peroxidation when compared to (S).

The underlying mechanism behind the variable cardiocytoprotective potentials of the studied antihypertensives are discussed and the impact of this on their clinical utility is raised. International Conference of: Infectious Diseases & Public Health. A research & Clinical Update Conference Hall, Alexandria, Egypt.

17-20 October 1997.

 

Do You Know That?
Therapeutic trends embark the use of;

Short-term high-dose combination of oral antioxidant supplementation [ 200 mg zinc sulphate, 500 mg of ascorbic acid 600 mg of tocopherol and 30 mg carotene I to hypertensives [ median basal SP being 165 nun Hg] for ~ weeks, aside their usual dietary! habits and regular unaltered.

Diagnostic Utilities Imply

Knowing the presence of a handy BP miniature monitor about the size of a deck of cards, that measures arterial pressure in left index finger by a process called "Photoelectric Oscillometry. It is called HEM-808F compact antihypertensives therapy, was able to significantly reduce blood pressure. This is possibly through achieved through increased availability of NO by removing superoxide anion. This may have implications for the innovative use of antioxidants as adjutants to conventional antihypertensive therapy.

Clin Sci 1997, 92, 361-5.

Finger blood pressure monitor. Also available, is another form that can be strapped around the wrist. These devices are only developed for people who keep close tabs on their blood pressure.

Modern Med Mid East 1997:14(6): :27.

 


EHS NEWS

The EHS newsletter has a new editorial hoard During the annual Ramadhan meeting of this year, Prof. Dr. M. Mohsen Ibrahim called upon all those who were interested to join. Dr. Mohammed Hamed remains our editor in chief Dr. Abdel Mooty El Keiy and Dr. Zeinab Ashour remains assistant editors. We would like to welcome the new members of the editorial board, Dr. Fawzia El Demerdasli, Professor of Cardiology, Mansoura University, Dr. Omnia Nayel, Professor of Pharmacology, Alexandria University. Dr. Alia Abdel Fattah. Assistant Professor of Critical Care Medicine, Cairo University and last hot not least. Magdy Saba, Cardiology, Resident at Cairo University.

CALENDAR

Assessment of vascular function, Background ,methods and clinical relevance Sophia Antipolis. France, 22-24 January 1998 Contact: European Heart house, 2035 route des Colles, les Templiers 06903 Sophia Antipolis Cedex

Tel 04 9294 7600

25th annual meeting of the Egyptian Society of Cardiology Cairo, Mariott Cairo, 22-27 February, 1998 Contact: Prof. Osama Abdel Aziz, 98 Mohammed Farid street.

 

Tel (202) 360 2800

23rd international joint conference on stroke Orlando, USA

 

5-7 February, 1998

Contact: American heart

 

association 7272, Greenville

Ave, Dallas TX 75231, USA

Tel (1-214) 706 11 00

 

The GlobaL Actions of Lacidipine
A new out look to matters, dears that a tenuous balance between steady state level of NO & reactive oxygen species [ROS] is essential to opdmize endothelial dependant vascular relaxation [EDVR], while any dismpthon in such balance predispose to dysfunction characteristic to many diseases as hypertension, atherosclerosis, diabetes, CHF.... etc.

Within this insight it was questioned, whether long term antihypertensive therapy targeted to normalize or at least improve endothelial dysfunction may reduce atherdsclerosis in hypertensives by virtue of such effect, or whether this is more obvious only by classes of antihypertensives possessing antiathero - sclerotic effects, as for example lacicipine.

No wonder, this drug was enrolled in the European Lacidipine Study on AtheroscIerosi,~ [ELSA] conducted on mild to moderate hypertensives whom were stratified according to the presence of carotid plaques or the presence or absence of intimd-medial carotid thickening. The objective was to contrast the effects of lacidipine versus atenolol on BP control [assessed by .ABPMJ. on carotid vessel progressive or retiressive modifications [assessed by B-mode ultra-sonography] & on incidence of CV events throughout a 5 years follow up period.

The metabolically neutral molecule of lacidipine was chosen, as it innovative characteristics. Thus, its high lipophilicity & binding affinity allows for prolonged contact to its specific receptors, while its high membrane partition coefficient permits its deep anchor in biomembranes to block the inactive site of Ca channels. This aside its ideal pharmacokinetics [peak:trough ratio

>6011/01, Mil all exert a potent, gradual, smooth, effective & sustained BP controls. By the same potentialities, it also exerts some anti atherogenic effects through blocking Ca dependent processes involved in plaque formation & progression as; cholesterol accumulation in macrophages, platelet aggregation, smooth muscle migration, proliferation & release of growth & chemotactic factors, ECM formation.., etc.

Beyond this, the unique structure & deep insertion of lacidipine in cell membranes permits its positioning near the double bonds most highly susceptible to peroxidative attack by ROS. This ranked the drug equipotent to Vit E as an antioxidant, to chain break autocatalytic alkoxyl & peroxyl radicle reactions, to prevent lipid peroxidat ion & to curtail LDL oxidation. minimizing its sequelac on plaque progression. Moreover this antioxidant capacity is abet to set back the balance of NO I ROS optimum enough to preserve EDYR thus controlling the vasomotor deficits characteristic to hypertension & atherosclerosis which contribute much to their clinical complications as; ischaemic LV dysfunction. AMI & CHF.

By highlighting such utilities, one can realize how lacidipine as 2-4mg once daily can globally encompass the pathobiological continuum of hypertension & atherosclerosis.

References:
Atherosclerosis 1989;80; 17-26
Free Radic Biol Mod 1992; 12:183-7.
J Cardiovasc Pharmacol 1995; 25(Suppl. 3) SI 1-6.
Biochem Pharn4 19%;51 (6);81 1-19.
Clin Cardiol 1997,20(11) [Suppl II]:11-17.
Clin Cardiol 1997,20 (11) [Supo II]:26-33.

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