Quinapril prevents hypertension and enhanced vascular reactivity in nitroarginine-treated rats

John R. Charpie, Peggy M. Charpie, Chetan Goud, Bertram Pitt, R. Clinton Webb

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Long-term inhibition of nitric oxide synthase (NOS) by substituted arginine analogues has previously been shown to induce systemic hypertension in several animal species; however, the precise mechanisms for the elevated blood pressure remain unclear. We hypothesized that a portion of the hypertensive response to arginine analogues was due to direct inhibition of endothelial NOS and resultant functional alterations in the vasculature that contribute to elevated systemic resistance. Adult Sprague-Dawley rats were treated for 2 weeks with an arginine analogue, N(ω)Nitro-L-arginine (L-NNA), alone or in combination with the angiotensin converting enzyme (ACE) inhibitor quinapril. Next, thoracic aortas were removed, cut into rings and suspended in isolated tissue baths for measurement of contractile force in response to vasoactive drugs. Our results showed that oral L-NNA treatment significantly elevated systolic blood pressure in rats that was completely prevented by quinapril. Furthermore, L-NNA treatment increased endothelium-dependent and -independent contractility and attenuated endothelium-dependent vasodilation in the thoracic aorta. These functional alterations were also attenuated by quinapril treatment. Therefore, long-term L-NNA-induced hypertension in rats is associated with enhanced vascular reactivity due both to direct inhibition of endothelial NOS and to stimulation of the renin-angiotensin system.

Original languageEnglish (US)
Pages (from-to)117-124
Number of pages8
JournalBlood Pressure
Volume6
Issue number2
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Nitroarginine
Blood Vessels
Arginine
Hypertension
Nitric Oxide Synthase Type III
Blood Pressure
Thoracic Aorta
Endothelium
Renin-Angiotensin System
Baths
Angiotensin-Converting Enzyme Inhibitors
Vasodilation
Nitric Oxide Synthase
Sprague Dawley Rats
Therapeutics
quinapril
Pharmaceutical Preparations

Keywords

  • angiotensin converting enzyme
  • endothelium
  • hypertension
  • nitric oxide synthase
  • vascular smooth muscle

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Quinapril prevents hypertension and enhanced vascular reactivity in nitroarginine-treated rats. / Charpie, John R.; Charpie, Peggy M.; Goud, Chetan; Pitt, Bertram; Webb, R. Clinton.

In: Blood Pressure, Vol. 6, No. 2, 01.01.1997, p. 117-124.

Research output: Contribution to journalArticle

Charpie, John R. ; Charpie, Peggy M. ; Goud, Chetan ; Pitt, Bertram ; Webb, R. Clinton. / Quinapril prevents hypertension and enhanced vascular reactivity in nitroarginine-treated rats. In: Blood Pressure. 1997 ; Vol. 6, No. 2. pp. 117-124.
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