Ryuji Sunagawa

Effect of intracoronary captopril on coronary blood flow and regional myocardial function in dogs.

To evaluate the cardiac effect of an inhibitor of angiotensin-converting enzyme, the effect of intracoronary (i.c.) captopril on coronary blood flow and regional myocardial function was examined in the anesthetized open-chest dog. Blood flow of the left circumflex coronary artery (LCX), left ventricular pressure (LVP), aortic pressure (AoP) and regional myocardial segment length were measured continuously. Captopril i.v. (0.3 mg/kg) produced an immediate reduction in AoP and an increase in percent shortening of myocardial segments followed by a decrease in coronary vascular resistance and increases in heart rate and LVdP/dt. Reductions in LCX flow induced by i.c. angiotensin were attenuated and i.c. bradykinin-induced increases in LCX flow were augmented after captopril. On the contrary, i.c. infusion of captopril (0.01 mg/min) into the LCX caused no change in hemodynamic variables and myocardial shortening although responses to angiotensin I and bradykinin were markedly modified. These results suggest that captopril may have no direct cardiac effect.

Vasodilating effects of nicorandil and nitroglycerin in anaesthetized open-chest dogs.

SummaryVasodilating effects of intravenous administrations of nicorandil (SG-75) and nitroglycerin were analyzed in anaesthetized open-chest dogs by measuring simultaneously, and continuously, coronary (CBF), vertebral (VBF), renal (RBF) and aortic blood flow (AoF). 1.Nicorandil 10–300 μg/kg i.v. and nitroglycerin 1–30 μg/kg i.v. decreased aortic blood pressure and increased CBF in a dose-dependent fashion.2.The doses of nicorandil and nitroglycerin which reduced coronary vascular resistance to about 60% of the predrug value were 100 μg/kg and 10 μg/kg, respectively.3.Nicorandil 100 μg/kg i.v. significantly increased AoF and heart rate, significantly decreased left ventricular enddiastolic pressure and did not significantly change VBF, RBF and left ventricular dP/dt. Nitroglycerin 10 μg/kg i.v. significantly increased VBF and heart rate, significantly decreased left ventricular end-diastolic pressure and produced an initial increase followed by a decrease in AoF and RBF.4.When compared with these doses of both drugs, the ratio of percent decrease in coronary vascular resistance to that in total peripheral resistance was over 1.0 in both drugs and the value of this ratio in nicorandil was significantly larger than that in nitroglycerin.5.The duration of increase in CBF produced by nicorandil 10–300 μg/kg i.v. was dose-dependent, but was not changed by nitroglycerin 1–30 μg/kg i.v. The results indicate that nicorandil and nitroglycerin dilate coronary vasculature more markedly than other vascular beds and that the potency of selective coronary vasodilatation and the duration of action are more significant in nicorandil than in nitroglycerin.

Effects of Beta-Adrenoceptor Blocking Agents on Myocardium Isolated from Experimentally Diabetic Rats

It is well known that patients with diabetes mellitus are frequently associated with atherosclerotic diseases such as hypertension and/or ischemic heart diseases (1–4). Recently, there are reports that some cases with diabetic cardiomyopathy have no obvious genesis but are accompanied with chronic congestive heart failure (5,6). In experimentally diabetic animals, it has been noted that chronotropic and inotropic actions of beta-adrenoceptor stimulating agents (beta agonists) diminished in isolated myocardium (7–9), and concomitant decrease in the number of beta-adrenoceptor might be responsible for these reduced myocardial functions (7–9). On the other hand, beta-adrenoceptor blocking agents (beta blockers) have generally been used for the therapy of hypertension and/or ischemic heart diseases accompanied with diabetes mellitus (10,11). When beta blockers are administered to patients with diabetic mellitus, their influences on lipids metabolism, hypoglycemia and/or secretion of insulin have been taken into account (12,13), but this is not the case with respect to myocardial function. If the decrease in the number of beta adrenoceptor is related to reduced myocardial function, then great attention must be paid to the use of beta blockers in diabetic patients. In the present study, therefore, to evaluate experimentally the influence of beta-blockers on diabetic myocardium, effects of propranolol with beta1 and beta2 adrenoceptor blocking activity as a standard beta blocker, and atenolol with beta1 adrenoceptor blocking activity as a cardioselective beta blocker on isoproterenol-induced responses of both atrial and papillary muscles isolated from experimentally diabetic rats were examined.

Effects of Autonomic Agents on Isolated and Perfused Hearts of Streptozotocin-Induced Diabetic Rats

Although it has been reported that myocardial contractility is reduced in diabetic animals (1–6), very little is known about cardiac responses to administered adrenergic and cholinergic agents. The present study, therefore, was designed to investigate the myocardial contractile response of perfused hearts isolated from experimental diabetic rats and insulin-treated diabetic rats to adrenergic and cholinergic agents.

Responses of Renal, Coronary and Vertebral Vasculatures to MC-838 and Captopril in Anesthetized Dogs

The regional hemodynamic effects of MC-838, a new angiotensin-converting enzyme inhibitor, and captopril at equidepressor doses were examined in the anesthetized dog by simultaneously measuring renal (RBF), coronary (CBF), vertebral (VBF) arterial and aortic blood flow (AoF). Hemodynamic responses to angiotensin I (AI), AII and noradrenaline were compared before and after the administration of each inhibitor. MC-838 (3 mg/kg i.v.) lowered gradually aortic pressure (AoP) and increased moderately AoF and RBF up to 60 min after the administration. Captopril (0.1 mg/kg i.v.) lowered AoP immediately after the administration and increased AoF and RBF more shortly than MC-838. Neither inhibitor produced a marked change in VBF or CBF. The effects of the inhibitors in the renal vascular bed was much greater than that in vertebral and coronary vascular beds, although vascular resistance in all of them was significantly reduced. Each of the drugs inhibited the pressor and renal vasoconstrictor responses to AI. These results indicate that the renal vasculature is more sensitive to both MC-838 and captopril than vertebral and coronary vasculature, but MC-838 has a slower and longer-lasting action than does captopril.