Hypertension alters the endothelial-dependent biphasic response of bradykinin in isolated Microminipig basilar artery.
Angiotensin (Ang) II is known to promote vascular disease and hypertension, partly through its effect on vascular endothelium. Bradykinin (BK) is an endothelium-dependent agonist that induces relaxation followed by contraction of the porcine basilar artery through release of NO and PGF2α, respectively. In this study, we evaluated the effect of Ang II-induced hypertension on basilar artery responsiveness to BK in the Microminipig (MMPig). Ang II (200ng/kg/min) or vehicle was infused into MMPigs for 14days using an osmotic mini-pump and blood pressure was monitored regularly. The responsiveness of subsequently isolated basilar arteries was then measured using a micro organ bath system. MMPig basilar artery endothelial cells were cultured and stimulated with Ang II or vehicle for 48h. Mean blood pressure was significantly (P<0.05; n=5) higher in Ang II-infused MMPigs than in vehicle-infused MMPigs. In vitro, BK-induced endothelium-dependent dilation of isolated basilar artery specimens was abolished and BK-induced contraction was significantly increased (Emax: 15.85±2.42% and 56.54±2.71% of 60mM KCl in control and Ang II group respectively at 10-7M concentration of BK; P<0.01; n=5) in Ang II-infused MMPigs. Ang II stimulation of the endothelial cells significantly decreased (54.15% at 24h; P<0.05; n=three independent experiment performed in triplicate) the amount of BK-elicited NO and increased (44.27% at 24h; P<0.05; n=three independent experiment performed in triplicate) the amount of BK-elicited PGF2α. These results suggest that the decrease of NO and increase of PGF2α production from endothelial cells are responsible for cerebrovascular dysfunction in hypertension, possibly causing cerebrovascular contraction and thus increasing the risk of brain infarction.
['Zahorul Islam|Md|M|', 'Kawaguchi|Hiroaki|H|', 'Miura|Naoki|N|', 'Miyoshi|Noriaki|N|', 'Yamazaki-Himeno|Emi|E|', 'Shiraishi|Mitsuya|M|', 'Miyamoto|Atsushi|A|', 'Tanimoto|Akihide|A|']
D000804:Angiotensin II D000818:Animals D062186:Arterial Pressure D001488:Basilar Artery D001920:Bradykinin D002478:Cells, Cultured D015237:Dinoprost D042783:Endothelial Cells D004730:Endothelium, Vascular D006973:Hypertension D066298:In Vitro Techniques D008297:Male D009569:Nitric Oxide D013552:Swine D013556:Swine, Miniature D014661:Vasoconstriction D014662:Vasoconstrictor Agents D014664:Vasodilation D014665:Vasodilator Agents
Hypertension Bradykinin Endothelium Angiotensin II Cerebral artery Nitric oxide Prostaglandin F(2α)