Ww. Pawlik et al., NITRIC-OXIDE AS MEDIATOR OF BRADYKININ-INDUCED PANCREATIC CIRCULATORYAND METABOLIC RESPONSES, Journal of Physiology and Pharmacology, 48(4), 1997, pp. 751-760
Bradykinin (BK) is an endogenous nonapeptide with potent vasodilator p
roperties of the visceral circulation. BK alters vascular tone via two
BK receptor subtypes, B-1 and B-2. Current experimental evidence sugg
ests that the dilator action of BK in some vessels is mediated primari
ly by B-2 receptor activation. In addition, there are reports that BK
increases endothelial generation of vasodilator factors, such as nitri
c oxide (NO). The present study had two aims. First, to explore the ro
le of BK-receptors in the pancreatic vasodilatatory and metabolic resp
onses to BK. Second aim was to examine whether endogenous NO play a ro
le in the mediation of BK-receptors induced pancreatic circulatory and
metabolic activity. In anesthetized dogs, the superior pancreatico-du
odenal artery blood flow (SPBF) was measured by ultrasonic blood flowm
eter (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 o
f the arteriovenous oxygen difference (AVO(2)) across the pancreatic c
irculation and SPBF. Drugs were infused into the superior pancreatico-
duodenal artery. BK (0.01-1.0 mg/kg/min) increased maximally SPBF by 1
80 +/- 15%, PBF by 208 +/- 22% and PVO2 by 145 +/- 11%, respectively.
Pretreatment with B-2-subtype receptor antagonist, D-Arg, [Hyp(3), Thi
(5,8), D-Phe(7)] BK inhibited significantly BK-induced increase in SPB
F, 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 hyp
eremic and metabolic responses. The results presented emphasize an imp
ortant role of B-2 receptors in the mediation of pancreatic circulator
y and metabolic responses to bradykinin. Endogenous NO plays a mediato
ry role in the pancreatic vascular and metabolic responses due to stim
ulation of B-2-receptors.