Bradykinin: potential for vascular constriction in the presence of endothelial injury.
Bradykinin (BK), a known vasodilator in vivo, and arginine vasopressin (AVP), a vasoconstrictor in vivo, both stimulate a rise in cytosolic free Ca2+ ([Ca2+]i) in vascular smooth muscle cells (VSMC). The present study was undertaken to investigate this apparent paradox. The following three possibilities were examined, namely, 1) signaling events other than [Ca2+]i are different for BK and AVP; 2) BK, but not AVP, stimulates prostaglandins in VSMC, thus resulting in divergent effects on VSMC tone; and 3) AVP and BK exhibit qualitatively similar effects on VSMC signal transduction but divergent effects on VSMC tone are mediated by endothelial events. The results demonstrated that BK stimulated a rise in inositol trisphosphate (IP3), [Ca2+]i, 45Ca2+ efflux, and Ca2+ influx and a biphasic change in intracellular pH when N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered solution was used. The BK-induced VSMC contraction was also comparable to that observed with AVP. The cyclooxygenase inhibitor, meclofenamate, enhanced the effect of both BK and AVP on VSMC tone, as assessed by shape change, by a comparable degree. BK, but not AVP, stimulated endothelial cells to release a substance that blocked the contractile response of BK and AVP. Methylene blue, a blocker of cytosolic guanylate cyclase and therefore of the production of guanosine 3',5'-cyclic monophosphate (2nd messenger of endothelium-derived relaxing factor, EDRF), and nordihydroguaiaretic acid, an inhibitor of EDRF, both prevented this endothelium-dependent effect of BK. These results therefore indicate that BK is a constrictor of VSMC, an effect that can be overridden by the hormone's endothelial effect to stimulate the release of a vasodilator(s), which is most likely EDRF.
Briner
V A
VA
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Tsai
P
P
Schrier
R W
RW
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D011453:Prostaglandins / Q000502:physiology; D015398:Signal Transduction; D014661:Vasoconstriction
D011453:Prostaglandins; D001127:Arginine Vasopressin; D001920:Bradykinin