Yasuyuki Shiraki

Cardiovascular effects of a new coronary vasodilator N-(2-hydroxyethyl)nicotinamide nitrate (SG-75): comparison with nitroglycerin and diltiazem.

Summary: The cardiovascular effects of a newly developed nicotinamide derivative. N-(2-hydroxyethy1)nicotinamide nitrate (SG-75). were examined in anesthetized, open-chest or closed-chest dogs and compared with those of nitroglycerin and diltiazem. When administered intra-arterially. SG-75 (0.003–1 mg) increased coronary, renal, mesenteric, and femoral blood flows in a dose-dependent fashion, without affecting systemic blood pressure or cardiac function. The coronary vasodilator response to SG-75 was not influenced by intra-arterial administration of propranolol, atropine, diphenhydramine, or dipyridamole. SG-75 (0.03–1 mg/kg) administered intravenously decreased systemic blood pressure and peripheral (coronary, renal, mesenteric, and femoral) vascular resistance and increased peripheral blood flow in a dose-dependent manner. In doses of 0.03–0.3 mg/kg. this drug did not significantly affect pulse pressure, heart rate, right atrial pressure, aortic blood flow, left ventricular (LV) pressure, LV dP/dt, or myocardial oxygen consumption. The results indicate that SG-75 has desirable characteristics as an antianginal agent.

Contribution of the tissue angiotensin converting enzyme to the antihypertensive effect of altiopril calcium (MC‐838) in spontaneously hypertensive rats

Abstract— The effect of a new orally active angiotensin converting enzyme (ACE) inhibitor, calcium (—)‐N‐[(S)‐3–[(N‐cyclohexylcarbonyl‐D ‐alanyl)thio]‐2‐methylpropionyl]‐L ‐prolinate (MC‐838, altiopril calcium), on systemic blood pressure (SBP) and tissue ACE activity has been examined in conscious spontaneously hypertensive rats (SHRs). MC‐838 (3 mg kg−1) given orally to SHRs elicited a long‐lasting hypotension lasting over 24 h. With the development of the hypotension, MC‐838 significantly reduced ACE activity in the lung, kidney and aorta, but not in the brain and heart. Suppression of plasma ACE and rise of plasma renin activity occurred only transiently at an earlier stage.

Enhancement of adenosine-induced relaxant responses of the guinea-pig isolated taenia coli and aortae by a novel nootropic agent BY-1949: comparison with dipyridamole

Abstract— In muscle strips of guinea‐pig taenia coli and aortae, the effects of 3‐methoxy‐1 1‐methyldibenz[b,f][1,4]oxazepine‐8‐carboxylate (BY‐1949) on the relaxant response to adenosine have been compared with those of dipyridamole. BY‐1949 (3 × 10−5–10−4 M) as well as dipyridamole (3 × 10−7–10−5 M) resulted in a significant potentiation of relaxant responses to a cumulative administration of adenosine (10−6–10−3 M), but the drugs did not affect the response to noradrenaline and acetylcholine. The results indicate that BY‐1949 exerts a selective potentiating effect on reactivity to exogenous adenosine.

CARDIOHAEMODYNAMIC EFFECTS OF LONG‐TERM INTRAVENOUS ADMINISTRATION OFW‐(2‐HYDROXYETHYL)NICOTINAMIDE NITRATE (SG‐75), A POTENT CORONARY VASODILATOR: COMPARISON WITH GLYCERYL TRINITRATE

1. Cardiohaemodynamic changes have been studied in beagle dogs treated with intravenous injections of either 300 μg/kg of N‐(2‐hydroxyethyl) nicotinamide nitrate (SG‐75) or 30 μg/kg of glyceryl trinitrate three times a day for 1 ‐2 months. Throughout the experimental period, no significant changes in general behaviour, body weights and plasma levels of enzymes and substrates were observed in either the SG‐75‐ or glyceryl‐trinitrate‐treated groups.

Comparative effects of ouabain on isolated papillary muscle from tree shrews, guinea‐pigs and rats

Abstract— Inotropic effects of ouabain were investigated in the isolated papillary muscle preparations of the tree shrew (Tupaiaglis), guinea‐pigs and rats. In the guinea‐pig and shrew papillary muscles, ouabain at concentrations of 10−8 to 3 × 10−7 M caused a concentration‐dependent positive inotropic response in a similar magnitude, while in the rat, ouabain at concentrations of 10−7 to 3 × 10−6 M elicited negative inotropic one. Either phentolamine or pindolol in a concentration sufficient to block the α‐ and β‐adrenoceptors did not antagonize the positive inotropic effect of ouabain in the papillary muscle preparation of the shrews.

Demonstration in Tupaia papillary muscle preparations of α‐adrenoceptors mediating positive inotropic effects: comparison with guinea‐pigs

1 Positive inotropic responses to α‐ and β‐adrenoceptor agonists of isolated papillary muscles from the tree shrew (Tupaia), were compared with those from guinea‐pigs. 2 In Tupaia, the concentration‐response curve for phenylephrine, unlike that for isoprenaline, was not affected by pindolol in a concentration (10−8m) sufficient to block β‐adrenoceptor‐mediated responses, but it was significantly shifted to the right by phentolamine (10−6m). In guinea‐pig papillary muscles, however, the concentration‐response curve for phenylephrine, like that for isoprenaline, was shifted to the right by pindolol (10−8m) but was unaltered by phentolamine (10−6m). Furthermore, when the mean concentrations of agonists inducing maximal positive inotropic responses were compared (relative to that of isoprenaline = 1.0), phenylephrine was found to be only slightly less potent (0.84 ± 0.04; n = 5) in Tupaia and much less potent (0.33 ± 0.06; n = 5) in the guinea‐pig. 3 Although in Tupaia papillary muscles the increase in developed tension induced by a combination of phenylephrine and isoprenaline did not significantly differ from that by phenylephrine alone, it was approximately 3 times larger than that produced by phenylephrine alone in guinea‐pigs. 4 These results indicate that in papillary muscles from Tupaia, unlike the guinea‐pig, the positive inotropic effects of phenylephrine can be mediated by α‐adrenoceptors.