Captopril and norepinephrine-induced hypertrophy and haemodynamics in rats.

Abstract

We wished to determine whether pretreatment with captopril, an angiotension-converting enzyme (ACE) inhibitor, modified the myocardial and haemodynamic consequences of chronic administration of norepinephrine (NE) in rats. Administration of NE (0.15 mg kg(-1) h(-1) by an osmotic minipump implanted subcutaneously for 28 days) resulted in left but not right ventricular hypertrophy. Captopril (250 but not 52 mu g kg(-1) h(1) administered for 28 days) significantly attenuated the development of left ventricular hypertrophy (weight of left ventricle to body weight ratio was 0.46 +/- 0.01 0.57 +/- 0.02, 0.53 +/- 0.02, and 0.51 +/- 0.01 for vehicle, NE, and NE plus low and high dose of captopril, respectively). Chronic administration of NE caused significant increases in systolic arterial blood pressure (BP: 194 +/- 11 vs. 130 +/- 6 mm Hg), systolic left ventricular pressure, heart rate (HR: 458 +/- 13 vs. 389 +/- 15 beats/min) and dP dt(-1)(max) P(-1), an index of myocardial contractility (202 +/- 29 vs. 91 +/- 3 s(-1)). Captopril (250 mu g kg(-1) h(-1) for 28 days) significantly reduced diastolic arterial BP (from 86 +/- 6 to 53 +/- 3 mm Hg). Concomitant administration of this dose of captopril together with NE prevented the NE-induced increase in systolic arterial BP but did not modify the increases in HR or dP dt(-1) max P(-1) (261 +/- 41 and 202 +/- 29 s(-1) in captopril and NE vs. NE-alone groups). Acute administration of NE (0.1-10 mu g kg(-1) intravenously, i.v.) produced less marked increases in cardiac contractility and in arterial BP in rats chronically pretreated with NE or NE plus captopril than in animals receiving vehicle or captopril alone. Chronic administration of NE and/or captopril did not significantly modify the haemodynamic effects of the acute administration of calcium chloride. We conclude that administration of captopril at 250 but not 52 mu g kg(-1) h(-1) for 28 days attenuates NE-induced cardiac hypertrophy and that this effect is associated with a decrease in systolic arterial BP. Captopril did not modify the reduced effects of acutely administered NE in rats treated with NE for a prolonged period.