CAPTOPRIL AND NOREPINEPHRINE-INDUCED HYPERTROPHY AND HEMODYNAMICS IN RATS

We wished to determine whether pretreatment with captopril, an angiote nsion-converting enzyme (ACE) inhibitor, modified the myocardial and h aemodynamic consequences of chronic administration of norepinephrine ( NE) in rats. Administration of NE (0.15 mg k(-1) h(-1) by an osmotic m inipump 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 developme nt of left ventricular hypertrophy (weight of left ventricle to body w eight 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 increas es in systolic arterial blood pressure (BP: 194 +/- 11 vs. 130 +/- 6 m m Hg), systolic left ventricular pressure, heart rate (HR: 458 +/- 13 vs. 389 +/- 15 beats/min) and dP dt(max)(-1) P-1, an index of myocardi al 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 WE prevented the NE-induced increase i n systolic arterial BP but did not modify the increases in HR or dP dt (max)(-1) 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) intr avenously, i.v.) produced less marked increases in cardiac contractili ty and in arterial BP in rats chronically pretreated with NE or NE plu s captopril than in animals receiving vehicle or captopril alone. Chro nic administration of NE and/or captopril did not significantly modify the haemodynamic effects of the acute administration of calcium chlor ide. We conclude that administration of captopril at 250 but not 52 mu g kg(-1) h(-1) fur 28 days attenuates NE-induced cardiac hypertrophy and that this effect is associated with a decrease in systolic arteria l BP. Captopril did not modify the reduced effects of acutely administ ered NE in rats treated with NE for a prolonged period.