Miyoharu Kobayashi

Positive chronotropic and inotropic effects of angiotension II in the dog heart

The effects of angiotensin II on sinus rate and atrial contractility were investigated in 17 isolated canine atria and 5 isolated paced ventricular preparations perfused with arterial blood conducted from a heparinized donor dog. When angiotensin II was injected into the cannulated sinus node artery, positive chronotropic responses were dose-dependently produced starting from the 0.01 microgram dose although inotropic responses to angiotensin II were not consistently induced. Angiotensin II produced a similar inotropic response pattern in the paced ventricular preparation. Moreover, when angiotensin II was given into the jugular vein of the donor dog, similar positive chronotropic and inotropic responses were also shown in the isolated atrium. Angiotensin II-induced positive chronotropic and slight inotropic effects were not influenced by treatment with the beta-adrenoceptor blocking agents, propranolol and carteolol, but significantly suppressed by saralasin which has been reported to be a competitive antagonist of angiotensin II. From these results, it is suggested that angiotensin II induced a positive chronotropic and slight positive inotropic effect via angiotensin II receptors in the dog heart.

Effects of disopyramide on SA nodal pacemaker activity and contractility in the isolated blood-perfused atrium of the dog.

The isolated blood-perfused preparations of canine atrium were suspended in a bath and perfused with arterial blood led from the carotid artery of the heparinized donor dog. Disopyramide caused dose-related negative chronotropic and inotropic effects in a dose range of 30-1000 microgram when injected directly into the cannulated sinus node artery of the isolated atrium. The order of potencies for inducing the negative chronotropic effect in isolated atrium preparations was verapamil greater than propranolol greater than lidocaine = quinidine greater than phenytoin greater than or equal to disopyramide greater than procainamide. On the other hand, the order of potencies for inducing the negative inotropic effect was verapamil = propranolol greater than lidocaine greater than or equal to phenytoin greater than disopyramide greater than procainamide greater than or equal to quinidine. When disopyramide (1 mg/kg or 3 mg/kg) was administered i.v. into the jugular vein of the donor dog, the systemic blood pressure of the donor dog was markedly decreased. However, the tension developed and sinus rate of the isolated atrium were only slightly decreased. Disopyramide produced greater suppression at higher frequencies and slightly depressed the calcium chloride-induced positive inotropic effects.

The effects of aminophylline on adenosine and ATP actions on sinoatrial conduction in the isolated, blood-perfused dog atrium

The effects of adenosine and adenosine triphosphate (ATP) on sinus cycle length (SCL) and sinoatrial conduction time (SACT) estimated by constant atrial pacing were studied in isolated, blood-perfused canine right atria. Adenosine and ATP were infused into the sinus node artery at a rate of 1, 2 and 4 micrograms/min. Both adenosine and ATP caused an increase in SCL and SACT in a dose-dependent manner and decreased atrial developed tension. There was no significant difference between the effect of adenosine and that of ATP on SCL and SACT. The prolongation of SACT induced by 4 micrograms/min of adenosine and ATP was significantly inhibited by a single injection of 1 to 3 mg of aminophylline, although this dose level of aminophylline did not significantly suppress the prolongation of SCL produced by adenosine and ATP. From these results it is concluded that both adenosine and ATP lengthen SCL and SACT in a dose-related manner, and that aminophylline blocks the increase in SACT much more easily than that in SCL.

DIFFERENTIAL CHRONOTROPIC AND INOTROPIC EFFECTS OF 2-NICOTINAMIDOETHYL NITRATE (SG-75) IN THE DOG ISOLATED ATRIUM

1. The chronotropic and inotropic effects of the anti‐anginal agent SG‐75 (2‐nicotinamidoethyl nitrate) and 1‐verapamil were investigated in isolated blood‐perfused canine atrial preparations. The compounds were administered via the cannulated sinus node artery.

Direct chronotropic and inotropic responses to guanosine and five different guanine nucleotides in isolated perfused dog atria

The effects of guanosine and of five guanine nucleotides on sinus rate and contractile force were investigated using the isolated, blood-perfused dog atrium preparation. Guanosine consistently induced a positive chronotropic and inotropic effect which was not suppressed by treatment with a potent beta-adrenoceptor blocking agent, carteolol. GMP, GDP and CTP induced a biphasic chronotropic and inotropic effect. The potencies for inducing the positive effects of GMP, GDP and GTP were almost the same. However, their rank order of potency for inducing negative effects was GTP greater than or equal to GDP greater than GMP. The negative responses to GTP were not inhibited by atropine. Cyclic GMP and dibutyryl cyclic GMP produced only slight negative chronotropic and inotropic effects but not consistently even at larger doses. The positive chronotropic and inotropic responses to norepinephrine were not modified by treatment with dibutyryl cyclic GMP.

Positive chronotropic and inotropic responses to guanosine in the isolated dog atrium

The effects of guanosine on chronotropism and inotropism in isolated dog atria were studied in spontaneously beating preparations which were suspended in a bath perfused with arterial blood from a carotid artery of a heparinized support dog. Guanosine administered into the cannulated sinus node artery in a dose range of 30 microgram to 3 mg produced a dose-related positive inotropic and chronotropic effect. The positive responses to guanosine were not inhibited by treatment with propranolol or a non-depressant beta-blocker, carteolol, in doses which blocked responses to norepinephrine. From these results, it is concluded that guanosine has a direct effect on atrial rate and contractility.