Comparison of the vasodilatory effects of bradykinin in isolated dog renal arteries and in buffer-perfused dog kidneys.
This study was undertaken to investigate the role of nitric oxide (NO), cyclooxygenase products and bradykinin (Bk) receptors in the Bk evoked responses of canine renal arteries and perfused kidneys. Rings of isolated canine renal arteries were mounted in organ chambers for measurement of isometric force. The isolated canine kidneys were perfused with Krebs-solution (constant flow) and the perfusion pressure was continuously recorded. The influence of the cyclooxygenase inhibitor indomethacin and the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginin (L-NOARG) on the vasocontractile responses to phenylephrine (PE) were examined in both preparations. Furthermore, the effects of Bk on the tone of canine isolated renal arteries and on the vasopressor responses of isolated buffer-perfused kidneys of dogs were tested in the absence and presence of enzyme inhibitors and the B2 kinin receptor antagonist HOE-140. It was found that indomethacin enhanced the contractile responses of large renal arteries to PE by 77 +/- 10%. In intact artery rings L-NOARG (0.1 mM) caused an additional potentiation of the PE-induced contractions in the presence of indomethacin (from 11.5 +/- 1.2 mN to 21.6 +/- 1.7 mN). However, L-NOARG failed to affect contractile responses to PE in endothelium-denuded rings. Bk produced a concentration-dependent relaxation of the precontracted endothelium-intact renal arteries. The IC50 value for Bk was 11.2 +/- 3.7 nM. The relaxant activity of the peptide in renal artery rings was not affected by indomethacin (3 microM). However, in the presence of L-NOARG a significantly higher concentration (IC50 = 860 +/- 300 nM) of Bk was required to relax renal arteries. The Bk receptor antagonist HOE-140 (10 nM for 40 min) attenuated the relaxant effect of Bk in renal artery rings (from an IC50 of 14.2 +/- 2.5 nM to 216 +/- 37 nM). Indomethacin (3 microM for 20 min) did not significantly alter the arteriolar vasoconstriction (from 45 +/- 4 mm Hg to 48 +/- 5 mm Hg, n = 5) evoked by PE. By contrast, L-NOARG (0.1 mM) potentiated (from 56 +/- 7 mm Hg to 94 +/- 11 mm Hg) the PE-induced vasopressor responses in perfused kidneys. Bk reduced the size of the pressor responses at relatively low concentrations (2-60 nM) but the dose-response curve was flat and the maximum inhibitory effect hardly exceeded 50 percent. Indomethacin (3 microM) did not modify the inhibitory effect of Bk in perfused kidney. In the presence of L-NOARG, Bk depressed the PE induced vasopressor effects with a maximum of 18 +/- 20%. Preincubation of the kidney preparations with the Bk antagonist HOE 140 (10 nM for 40 min) almost completely abolished the inhibitory effect of Bk on the PE induced vasopressor responses. The results suggest that the endothelial NO plays a fundamental role in the relaxant effect of Bk and considerably modulates vascular reactivity to PE in canine renal vasculature. Furthermore, significant difference exists between conduit and resistance vessels of dog's kidney in the effect of indomethacin on the adrenergic contractions.
Malomvölgyi
B
B
Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
Hadházy
P
P
Tekes
K
K
Koltai
M Z
MZ
Pogátsa
G
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002021:Buffers; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010477:Perfusion; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012077:Renal Artery / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D002021:Buffers; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D019335:Nitroarginine; C065679:icatibant; D019001:Nitric Oxide Synthase; D001920:Bradykinin; D007213:Indomethacin