[Effects of new antihypertensive agent, 2-[4-(n-butyryl)-homopiperazine-1-ul]-4-amino-6, 7-dimethoxy-quinazoline (E-643), on blood pressure, urinary sodium excretion and urinary norepinephrine excretion rate in stroke-prone, spontaneously hypertensive rats].
Present study was undertaken to elucidate the effects of E-643, on blood pressure, urinary electrolyte (U-Na, U-K) and catecholamines excretion rates in stroke-prone spontaneously hypertensive rats (SHRSP). An attempt was also made to clarify the effects of E-643 on plasma catecholamine concentration and sympathetic efferent nerve discharges including renal and adrenal nerve activity. E-643 (10 mg/kg/day X 4 weeks, p.o.) administered SHRSP (E-643 SHRSP) produced a significant hypotensive effect as compared with sex-age matched nondrug control SHRSP (control SHRSP). Both U-Na and U-K in E-643 SHRSP increased significantly as compared with those of control SHRSP. Urinary norepinephrine content (U-NE) also increased significantly in E-643 SHRSP. Plasma NE concentration tended to increase in E-643 SHRSP. While, plasma epinephrine (E) concentration decreased significantly in E-643 SHRSP. E-643 did not produce any significant effects on both sympathetic renal nerve activity and adrenal nerve activity in SHR. The changes induced by exogenous administered NE (blood pressure rise, tachycardia and the change in sympathetic nerve activity) were antagonized by pretreatment of E-643 in SHR. It was demonstrated that therapeutic doses of E-643 did not seem to produce any significant effect on central nervous system. These findings suggest that E-643 is a peripherally acting alpha 1 antagonist with natriuretic effect.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D002561:Cerebrovascular Disorders / Q000209:etiology; D004435:Eating / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009638:Norepinephrine / Q000652:urine*; D011188:Potassium / Q000652:urine; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D002395:Catecholamines; D011799:Quinazolines; C018176:bunazosin; D011188:Potassium; D009638:Norepinephrine