Increased nitric oxide accounts for decreased basal vascular tone and responsiveness in the resistance vessels of high-cholesterol-fed rabbits.

Abstract:

:The objective of this study was to determine the effects of hypercholesterolemia on basal vascular tone and vascular responses to pharmacologic agents in hindquarter resistance vessels. Blood pressure and hindquarter blood flow were measured in conscious rabbits fed a high cholesterol diet (1%) for 17 weeks (HC) compared to age-matched rabbits fed a normal diet (control). Basal hindquarter blood flow and vascular conductance were significantly higher in HC than in control rabbits. Administration of a non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (100 mg/kg) decreased basal hindquarter blood flow and vascular conductance in a greater magnitude in HC than in control rabbits, thus, abolished the differences in both the flow and conductance between 2 groups, indicating that increased NO was responsible for reduced basal vascular tone in the HC rabbits. L-NIL (30 mg/kg), a selective inducible NOS (iNOS) inhibitor had no effects on either flow or conductance. This result does not support the involvement of iNOS. In separate experiments, animals were anesthetized and instrumented with an extracorporeal circuit to measure perfusion pressure under constant blood flow to the hindquarter vascular bed. In the HC group, vascular responses to acetylcholine, S-nitroso-N-acetyl-penicillamine and phenylephrine were all attenuated when compared to the responses in the control rabbits. These results indicate that local overproduction of NO due to hypercholesteremia could desensitize smooth muscle reactivity, thus causing general vascular hyporesponsiveness to vasoactive agents.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Fitch R,Da Cunha V,Kauser K,Dole W,Parkinson J,Vergona R,Sullivan ME,Wang YX

doi

10.1159/000056137

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

220-7

issue

4

eissn

0031-7012

issn

1423-0313

pii

pha63220

journal_volume

63

pub_type

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