Cardiovascular and electrophysiological analysis of a selective vasodilatory prostacyclin analogue, 5-nitro-PGI1.
5-nitro-PGI1 is a selective vasodilatory analogue of prostacyclin which has not antiaggregatory potency. We examined the hemodynamics, antiaggregatory and electrophysiological effects of 5-nitro-PGI1, comparing them with those of PGI2-Na and nitroglycerin (NG). In anaesthetized open-chest cat and dog, PGI2-Na, 5-nitro-PGI1 and NG reduced the mean blood pressure (BP), BPsyst, BPdiast, left ventricular pressure, dp/dtmax, coronary resistance, while their effect on heart rate, on cardiac output was inconsistent. ED50 values of BP lowering effect of PGI2-Na, 5-nitro-PGI1 and NG were 4.6 X 10(-10), 3.9 X 10(-10) and 6 X 10(-10)(M), respectively. IC50 values on ADP (10 microM) induced aggregation in rabbit platelet rich plasma of PGI2-Na, 5-nitro-PGI1 and NG were 5 X 10(-9), 3.5 X 10(-4), 3.75 X 10(-3) (M), respectively. The transmembrane action potential (AP) characteristics were not changed significantly by 10(-6)M 5-nitro-PGI1. Higher concentrations (10(-5), 10(-6)M) slightly reduced the resting potential (RP) and maximum rate of rise (Vmax) of AP and shortened AP duration. NG in 10(-6)M caused a slight hyperpolarization, while higher concentrations (10(-5), 10(-4)M) shortened only AP duration. PGI2-Na in all concentration studied (1.6 X 10(-6) -10(-4)M) caused a slight hyperpolarization, increased potently Vmax but shortened AP duration only in high concentration. The results show that 5-nitro-PGI1 exerted the same hemodynamic effect as PGI2-Na and NG; practically failed to exert antiaggregatory activity; and had similar electrophysiological effects to NG.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D002415:Cats; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D009599:Nitroprusside; C043868:5-nitroprostaglandin I1; D011464:Epoprostenol; D005996:Nitroglycerin