Cytochrome P450 and Cyclooxygenase Metabolites Contribute to the Endothelin-1 Afferent Arteriolar Vasoconstrictor and Calcium Responses

摘要: Arachidonic acid metabolites contribute to the endothelin-1 (ET-1)-induced decrease in renal blood flow, but vascular sites of action are unknown. Experiments performed vitro used rat juxtamedullary nephron preparation combined with videomicroscopy. The response afferent arterioles ET-1 was determined before and after cytochrome P450 (CYP450) or cyclooxygenase (COX) inhibition. Afferent arteriolar diameter averaged 20+/-1 microm (n=17) at a perfusion pressure 100 mm Hg. Superfusion 0.001 10 nmol/L caused graded arteriole. Vessel decreased by 30+/-2% 41+/-2% 1 ET-1, respectively. significantly attenuated during administration CYP450 hydroxylase inhibitor N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), such that 19+/-3% 22+/-3% COX inhibition also greatly vasoconstriction elicited whereas epoxygenase N-methylsulfonyl-6-(2-proparglyoxyphenyl) hexanamide enhanced ET-1-mediated response. Additional studies were using freshly isolated smooth muscle cells prepared from preglomerular microvessels. Renal microvascular loaded calcium-sensitive dye fura 2 studied use single-cell fluorescence microscopy. Basal cell [Ca(2+)](i) 95+/-3 (n=42). (10 nmol/L) increased peak value 731+/-75 stabilizing 136+/-8 nmol/L. Administration DDMS indomethacin calcium ET-1. These data demonstrate arachidonic importantly responses