Dose-Related Changes in the Mechanical Properties of the Carotid Artery in WKY Rats and SHR following Relaxation of Arterial Smooth Muscle

Abstract

Acute converting enzyme inhibition relaxes arterial smooth muscle and increases arterial complicance in several models of animal and human hypertension. However, it is unknown whether the doses needed for the relaxation of large arteries are similar to those inducing arteriolar relaxation and blood pressure (BP) decrease. To answer this question, we used a previously described model of the in situ carotid artery to determine the pressure-volume relationship over a range of transmural pressures from 25 to 200 mm Hg in normotensive rats (WKY) and spontaneously hypertensive rats (SHR). The pressure-volume relation was determined after an acute single oral administration of either a placebo or the converting enzyme inhibitor quinapril given at two different doses (0.3 or 3 mg/kg). At the end of each experiment, the total relaxation of arterial smooth muscle was achieved after a local administration of potassium cyanide (KCN). In the WKY placebo group, from 25 to 100-125 mm Hg transmural pressure, carotid compliance increased and reached a maximum value at 100-125 mm Hg (i.e. close to the operating range of systemic mean BP of the animals), and decreased thereafter. In the SHR placebo group, carotid compliance was significantly lower than in the WKY placebo group for transmural pressure up to 125 mm Hg, and thereafter was equal or even higher; the maximum value of compliance was reached at 125-150 mm Hg transmural pressure, i.e. substantially less than the operating range of the systemic mean BP of the SHR placebo (180 mm Hg). For transmural pressure steps up to 100 mm Hg in WKY and 125 mm Hg in SHR, both doses of quinapril produced an identical relaxation of arterial smooth muscle which approximated 80-90% of the maximum relaxation produced by KCN. For higher transmural pressure levels, neither quinapril nor KCN were able to change compliance values. Although the two doses caused the same degree of arterial smooth muscle relaxation in SHR, operating carotid compliance was substantially increased only with the higher dose, i.e. the dose which significantly shifted the operating systemic BP towards normotensive levels. The study provides evidence that, although low, nonhypertensive doses of quinapril are able to induce maximal relaxation of the carotid artery, operating compliance is substantially increased only if blood pressure is significantly decreased.