title: Calcium signaling mechanisms in renal vascular responses to vasopressin in genetic hypertension.
abstract: Previous blood flow studies demonstrated that arginine vasopressin (AVP) produces exaggerated renal vasoconstriction in young spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto control rats (WKY). The purpose of the present study was to determine the role of postreceptor calcium signaling pathways in AVP-induced renal vasoconstriction in vivo. Renal blood flow (RBF) was measured by electromagnetic flowmetry in anesthetized, water-loaded, 8-week-old WKY and SHR pretreated with indomethacin to avoid interactions with prostaglandins. AVP was injected into the renal artery to produce a transient 25% to 30% decrease in RBF without affecting arterial pressure. To achieve similar control levels of vasoconstriction, SHR received a lower dose (2 versus 5 ng). Coadministration of nifedipine with AVP produced dose-dependent inhibition of the AVP-induced renal vasoconstriction. Nifedipine exerted maximum inhibition by blocking 30% to 35% of the peak AVP response, indicating the involvement of dihydropyridine-sensitive voltage-dependent calcium channels. To evaluate intracellular calcium mobilization, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) or heparin was coadministered with AVP. Each agent produced a dose-dependent inhibition of up to 65% of the maximum blood flow change produced by AVP. The degrees of inhibition produced by maximum effective doses of nifedipine and TMB-8 were additive; the combination blocked up to 85% of the response to AVP. These observations indicate that about one third of the AVP-induced constriction of renal resistance vessels is mediated by voltage-dependent L-type calcium channels responsive to the dihydropyridine nifedipine. Approximately two thirds of the change in vascular tone is due to inositol 1,4,5-trisphosphate-mediated calcium mobilization from intracellular sources sensitive to TMB-8 and heparin. The results suggest that the exaggerated renal vascular reactivity to AVP challenge in SHR is probably not due to a strain difference in postreceptor calcium signal transduction. After AVP receptor stimulation, calcium mobilization and calcium entry signaling pathways participate to similar degrees in WKY and SHR.
authors.affiliation: Department of Physiology, University of North Carolina at Chapel Hill 27599-7545, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Feng
authors.forename: W J
authors.initials: WJ
authors.lastname: Arendshorst
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D006493:Heparin; D009543:Nifedipine; D002118:Calcium