Role of prostanoids in renin-dependent and renin-independent hypertension.
We investigated the role of prostanoid-mediated pressor mechanisms in setting the level of blood pressure in renin-dependent and renin-independent models of hypertension in unanesthetized rats. Intravenous administration of a blocker of thromboxane A2/prostaglandin endoperoxide receptors, SQ29548 (2 mg/kg bolus injection plus 2 mg/kg/hr for 3 hours), reduced from 162 +/- 4 to 144 +/- 5 mm Hg (p less than 0.05) the blood pressure of rats with aortic coarctation-induced hypertension at 7-14 days after coarctation when plasma renin activity is greatly increased. In contrast, treatment with SQ29548 was without effect on the blood pressure of either normotensive or hypertensive rats (i.e., aortic coarctation-induced hypertension at 90-113 days after coarctation, deoxycorticosterone-salt-induced hypertension) having normal or depressed values of plasma renin activity. The blood pressure-lowering effect of SQ29548 in the early phase of aortic coarctation-induced hypertension was positively correlated with the prevailing plasma renin activity and could not be demonstrated in hypertensive rats pretreated with indomethacin. We attribute the hypotensive effect of SQ29548 to interference with pressor mechanisms that depend on activation of thromboxane A2/prostaglandin endoperoxide receptors and suggest that such prostanoid-mediated mechanisms are operational and contribute to an increase in blood pressure in angiotensin-dependent forms of hypertension. Also prostanoid-mediated vasodepressor mechanisms are operational in the early phase of aortic coarctation-induced hypertension since the blood pressure of rats pretreated with SQ29548 was increased by the subsequent administration of indomethacin. Accordingly, the blood pressure of rats with aortic coarctation-induced hypertension is influenced by the interplay of prostanoid-mediated pressor and vasodepressor mechanisms.
Lin
L
L
Department of Pharmacology, New York Medical College, Valhalla.
Mistry
M
M
Stier
C T
CT
Nasjletti
A
A
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism / Q000652:urine; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003900:Desoxycorticosterone; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D012083:Renin / Q000097:blood / Q000502:physiology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D013929:Thromboxane B2 / Q000378:metabolism / Q000652:urine
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011453:Prostaglandins; D011982:Receptors, Prostaglandin; C055662:prostaglandin endoperoxide receptor; D003900:Desoxycorticosterone; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C045749:SQ 29548; D012083:Renin