Prostanoid response in the kidney of hypertensive subjects as part of renal counteraction to gallopamil-induced blood pressure decrease.
The purpose of the study was to characterize the renal TxA2, PGI2 and PGF2 alpha release in response to arterial blood pressure (BP) fall induced by systemic and intrarenal vasorelaxation in subjects with essential hypertension. Significantly enhanced TxB2- and PGF2 alpha excretion and no change in ratio TxB2/6-keto-PGF1 alpha were found in urine in hypertensive patients after administration of the Ca++ entry blocker gallopamil, used to induce BP fall. This response was associated with significant PRA elevation in peripheral venous samples. In in vitro experiments, direct and indirect effects of gallopamil on renal tissue could be distinguished. Gallopamil resulted in significant diminution of TxA2 production and a decrease in TxB2/6-keto PGF1 alpha ratio in incubated rat kidney slices. This model was also used to test biochemically the effect of reflex sympathetic activation on prostanoid generation in kidney. It was concluded that this mechanism was only one among the indirect mechanisms by which gallopamil could induce that renal prostanoid response in hypertensive subjects. The response in urinary TxB2- and PGF2 alpha excretion was found to be significantly related to the changes in sodium reabsorption. These results suggested, that the increase in renal TxA2 and PGF2 alpha production in response to systemic and intrarenal "vasodilation" induced by gallopamil in hypertensive subjects can be interpreted as part of counteraction of the kidneys to BP fall.
Székács
B
B
Second Department of Medicine, Semmelweis University Medical School, Budapest, Hungary.
Juhász
I
I
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000652:urine*; D000328:Adult; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015237:Dinoprost / Q000097:blood / Q000652:urine*; D005260:Female; D005711:Gallopamil / Q000494:pharmacology / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism; D013929:Thromboxane B2 / Q000097:blood / Q000652:urine*
D005711:Gallopamil; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D012964:Sodium; D015237:Dinoprost; D012083:Renin; D009638:Norepinephrine