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Antihypertensive pharmaceutical effects of different pharmacologic classrooms on the functional and structural hair rarefaction in spontaneously inbred rats.

by Sabino, Bruno Duarte

Abstract (Summary)
Introduction: It is well known that the major part of the increased vascular resistance in hypertension isdetermined at the microvascular level, resulting mainly from functional (changes in vascular reactivity) and/orstructural (increased arteriolar wall thickness) abnormalities. We investigated the effects of chronic oralantihypertensive treatment on functional and structural capillary rarefaction in spontaneously hypertensive rats(SHR). Wistar Kyoto rats (WKY) were used as a normotensive control group. Methods: Male SHR (12-14weeks) received oral treatment with the ß-blocker atenolol (ATE) (50 mg/kg/day), angiotensin-convertingenzyme (ACE) inhibitor enalapril ENA (10 mg/kg/day), the calcium channel blocker nifedipine NIF(20mg/kg/day), the angiotensin II type I receptor (AT1) receptor antagonist losartan LOS (10mg/kg/day), orvehicle (control group) during four weeks. At the end of the treatment, the functional capillary density (FCD) wasevaluated by intravital videomicroscopy with fluorescence. Then, we evaluated the structural capillary density(SCD) by immunohistochemistry embedded in paraffin. Results: In untreated rats, the FCD was lower in SHRskeletal muscle (WKY 395±17 and SHR 258±13 capillaries/mm2, Plt;0.01) and ear skin (WKY 391±18 and SHR210±15 capillaries/mm2, Plt;0.01). A linear relationship was seen between skeletal muscle and skin capillarydensities (r=0.654, Plt;0.0001). Histologic analysis showed that SHR had a lower capillary-to-fiber ratio in theskeletal muscle (WKY 1.74±0.08 and SHR 1.40±0.06, Plt;0.01). Capillary volume density-to-fiber volumedensity ratio in the left ventricle of SHR was also reduced (WKY 0.55±0.09 and SHR 0.42±0.09, Plt;0.01). Thepharmacological treatment with ENA, LOS, ATE, or NIF, resulted in similar reductions in systolic bloodpressure (19.8%, 19.1%, 17.4%, and 18.2%, respectively, Plt;0.05). ATE did not induce any change in functionalcapillary density of SHR. LOS and NIFE completely reversed functional capillary rarefaction in both muscle andcutaneous tissues (434±26 and 422±18 capillaries/mm2 in skeletal muscle and 397±31 and 391±24capillaries/mm2 in skin, plt;0,01, respectively), whereas ENA significantly increased functional capillary densityonly in the skin. The skeletal muscle capillary-to-fiber ratio was normalized by ENA, LOS, and NIF (1,65±0,04;1,78±0,1 and 1,8±0,07, plt;0,01, respectively). Treatments with ENA or LOS normalized the cardiac structuralcapillary rarefaction of SHRs (0,59±0,03 and 0,59±0,03, plt;0,01, respectively), whereas ATE and NIF had noeffect. Discussion: Our results suggest that different pharmacologic classes of antihypertensive drugs with similareffect on blood pressure differ in terms of their effect on the microcirculation. This concept could be useful toguide the pharmacological treatment of hypertension, in order to reduce or even revert the target organ damage.
This document abstract is also available in Portuguese.
Bibliographical Information:

Advisor:Eduardo Vera Tibiriçá

School:Faculdades Oswaldo Cruz

School Location:Brazil

Source Type:Master's Thesis

Keywords:Antihypertensive Agents Rats Inbred SHR Microcirculation Target Organs FARMACOLOGIA CARDIORENAL

ISBN:

Date of Publication:05/16/2008

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