Influences of carvedilol treatment on the effects of acetylcholine on regional haemodynamics in the spontaneously hypertensive rat

Abstract

1. In a previous report, we have shown that vasodilatation induced by acetylcholine is impaired in the kidney and the heart of the spontaneously hypertensive rat (SHR) in vivo. The present investigation was performed to study the influence of oral antihypertensive treatment with carvedilol for 6 to 10 weeks on acetylcholine-induced changes in regional haemodynamics in SHR in vivo. Cardiac output, regional blood flow and vascular resistance in organs of major importance in hypertensive disease, such as the kidney, heart, skeletal muscle, brain and eye, were measured with radioactively labelled microspheres in anaesthetized rats (aged 12-16 weeks).2. Mean arterial blood pressure was significantly lower in the carvedilol-treated SHR group (156+/-3 mmHg, n=17) than in an untreated SHR group (172+/-6 mmHg, n=13). Infusion of acetylcholine (2 microgram.min-1.kg-1) caused similar significant reductions in blood pressure in the two groups (-13+/-1% and -14+/-2%). However, acetylcholine induced a significant increase in total peripheral vascular resistance in the carvedilol group (29+/-10%, P<0.01), whereas no significant change was observed in the control group (0+/-11%).3. Acetylcholine significantly increased renal vascular resistance in the carvedilol group (+62+/-15%, P<0.01), but did not change vascular resistance in the control group (-6+/-6%). In the heart, acetylcholine did not affect vascular resistance in the carvedilol group, but reduced vascular resistance significantly in the control group (-17+/-8%, P<0.05). The circulatory changes induced by acetylcholine in the skeletal muscle, brain and ophthalmic circulation did not differ between the groups.4. In conclusion, the results demonstrate that long-term oral carvedilol treatment in the SHR did not enhance acetylcholine-induced vasodilatation, but instead pronounced renal vasoconstriction was induced by acetylcholine, which could partly be due to a decreased cardiac index.