Nitric oxide as mediator of bradykinin-induced pancreatic circulatory and metabolic responses.
Bradykinin (BK) is an endogenous nonapeptide with potent vasodilator properties of the visceral circulation. BK alters vascular tone via two BK receptor subtypes, B1 and B2. Current experimental evidence suggests that the dilator action of BK in some vessels is mediated primarily by B2 receptor activation. In addition, there are reports that BK increases endothelial generation of vasodilator factors, such as nitric oxide (NO). The present study had two aims. First, to explore the role of BK-receptors in the pancreatic vasodilatatory and metabolic responses to BK. Second aim was to examine whether endogenous NO play a role in the mediation of BK-receptors induced pancreatic circulatory and metabolic activity. In anesthetized dogs, the superior pancreatico-duodenal artery blood flow (SPBF) was measured by ultrasonic blood flowmeter (Transonic System T-206), pancreatic microcirculatory blood flow (PBF) was determined by laser Doppler flowmetry (Periflux 4001 Master). Pancreatic oxygen consumption (PVO2) was calculated as the product of the arteriovenous oxygen difference (AVO2) across the pancreatic circulation and SPBF. Drugs were infused into the superior pancreatico-duodenal artery. BK (0.01-1.0 mg/kg/min) increased maximally SPBF by 180 +/- 15%, PBF by 208 +/- 22% and PVO2 by 145 +/- 11%, respectively. Pretreatment with B2-subtype receptor antagonist, D-Arg, [Hyp3, Thi5,8, D-Phe7] BK inhibited significantly BK-induced increase in SPBF, PBF and PVO2 by 86 +/- 8%, 73 +/- 7% and 85 +/- 6%, respectively. A nitric oxide synthesis inhibitor (L-NNA) administered i.v. at dose of 25 mg/kg 20 min before BK, inhibited significantly the pancreatic hyperemic and metabolic responses. The results presented emphasize an important role of B2 receptors in the mediation of pancreatic circulatory and metabolic responses to bradykinin. Endogenous NO plays a mediatory role in the pancreatic vascular and metabolic responses due to stimulation of B2-receptors.
Pawlik
W W
WW
Department of Physiology, Jagiellonian University School of Medicine, Cracow, Poland.
Sendur
R
R
Biernat
J
J
Kozioł
R
R
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000187:drug effects
D018002:Receptors, Bradykinin; D009569:Nitric Oxide; D001920:Bradykinin