Mechanism of action of a new prostaglandin antihypertensive, viprostol [CL 115 347; (dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester]: (II). Effects on the adrenergic nervous system.
Viprostol [(dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester; CL 115 347] is a new orally and transdermally active antihypertensive agent that exerts its major antihypertensive action by vasodilation. The present studies were conducted to examine its effects on the adrenergic nervous system. In cats, viprostol did not inhibit renal sympathetic nerve discharge (RSND) monitored at the postganglionic region, indicating that nerve transmission or conduction was not blocked at the ganglion or the pre- or postganglionic fibres. In cat nictitating membrane preparations in situ, viprostol partially blocked the membrane contractile response to exogenous epinephrine and norepinephrine, as well as to electrical stimulation of pre- and postganglionic fibres. In spontaneously hypertensive rats (SHR), viprostol partially blocked the vasopressor response of exogenous norepinephrine and epinephrine specifically without influencing that of angiotensin II. All these suggest that viprostol produced weak alpha-adrenoceptor blockade. Viprostol did not antagonize the tachycardia induced by stimulation of the discrete segments at C7-T1 (cardio-accelerator) of the spinal cord in pithed SHR, suggesting that viprostol did not activate the presynaptic alpha-adrenoceptors. Viprostol significantly inhibited the increase in blood pressure induced by electrical stimulation of the spinal cord at T7-T9 in pithed SHR, probably due to postsynaptic alpha-adrenoceptor blockade. In conclusion, viprostol produced weak, but statistically significant alpha-adrenoceptor blockade which may contribute partially to its antihypertensive action.
D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002714:Chlorisondamine / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives*; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009541:Nictitating Membrane / Q000187:drug effects / Q000294:innervation; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011941:Receptors, Adrenergic / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013610:Tachycardia / Q000188:drug therapy / Q000503:physiopathology
D006584:Hexamethonium Compounds; D011453:Prostaglandins; D011459:Prostaglandins E, Synthetic; D011941:Receptors, Adrenergic; D018738:Hexamethonium; D004246:Dimethylphenylpiperazinium Iodide; D000803:Angiotensin I; D002714:Chlorisondamine; D015232:Dinoprostone; C034232:viprostol; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine