Dose-related changes in the mechanical properties of the carotid artery in WKY rats and SHR following relaxation of arterial smooth muscle.
Acute converting enzyme inhibition relaxes arterial smooth muscle and increases arterial compliance 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Benetos
A
A
Department of Internal Medicine, INSERM U-337, Paris, France.
Pannier
B
B
Brahimi
M
M
Safar
M E
ME
Levy
B I
BI
D000818:Animals; D001794:Blood Pressure; D002339:Carotid Arteries / Q000187:drug effects*; D003187:Compliance / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy; D007546:Isoquinolines / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077583:Quinapril