Captopril and norepinephrine-induced hypertrophy and haemodynamics in rats

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

Streptozotocin diabetes protects against arrhythmias in rat isolated hearts: role of hypothyroidism

We examined the contribution of hypothyroidism to streptozotocin diabetes-induced alterations in the arrhythmia susceptibility of ex vivo hearts to regional zero-flow ischaemia. Diabetic rats received either protamine zinc insulin (10 IU/kg/day, s.c.) or triiodothyronine (10 microg/kg/day, s.c.) for 8 weeks commencing 72 h after injection of streptozotocin (60 mg/kg, i.p.). Arrhythmias were determined in ex vivo Langendorff-perfused hearts, subjected to a 30-min main left coronary artery occlusion, followed by 30-min reperfusion. Serum free thyroxine concentrations, rectal temperature and ex vivo heart rate were significantly decreased in the 8-week diabetic group

Phosphodiesterase isozymes from the hearts of dogs subjected to cardiac pacing

Myocardial biopsy samples were taken from dogs 24 h after a period of rapid right ventricular pacing and analyzed for the presence of various isoforms of phosphodiesterase (PDE). Rapid cardiac pacing resulted in marked protection against ventricular arrhythmias (reduction in ventricular fibrillation from 60% to 10%), but no changes in PDE-specific activities were determined in these crude homogenates towards cAMP and cGMP in either the presence (stimulated activities) or the absence (basal activities) of calmodulin in both control and paced tissues. Basal cAMP hydrolytic activity was 1.7-fold more marked than the corresponding cGMP hydrolytic activity determined in the same sample. The relative proportions of PDE2, PDE3 and PDE4 in control and paced hearts were similar and for control hearts were 37.0±3%, 34.8±2.4% and 16.7±2.7%, respectively, for total cAMP hydrolytic activity. The major cGMP hydrolytic activity was PDE1 (73.8±1.4%) with the remainder ascribed to PDE2 and PDE3. It is concluded that the induction of PDE enzymes does not take place following cardiac pacing and does not account for the marked antiarrhythmic effects of this form of preconditioning