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. 1995 Jan;114(1):99–102. doi: 10.1111/j.1476-5381.1995.tb14911.x

Cytochrome P450-dependent effects of bradykinin in the rat heart.

D Fulton 1, K Mahboubi 1, J C McGiff 1, J Quilley 1
PMCID: PMC1510183  PMID: 7712035

Abstract

1. Vasodilator responses to bradykinin (BK) in the rat heart are reported to be independent of NO and cyclo-oxygenase/lipoxygenase products of arachidonic acid (AA). 2. We verified that inhibition of NO synthase with L-nitroarginine (50 microM) and cyclo-oxygenase with indomethacin (2.8 microM) were without effect on vasodilator responses to BK (10-1000 ng) in the Langendorff rat heart preparation. 3. L-Nitroarginine elevated perfusion pressure, signifying a crucial role of NO in the maintenance of basal vasculature tone. 4. In hearts treated with L-nitroarginine to eliminate NO and elevate perfusion pressure, vasodilator responses were reduced by inhibitors of cytochrome P450 (P450), clotrimazole (1 microM) and 7-ethoxyresorufin (1 microM). 17-Octadecynoic acid (17-ODYA 2 microM), a mechanism based inhibitor of P450-dependent metabolism of fatty acids, also reduced vasodilator responses to BK. 5. These results confirm that NO and prostaglandins do not mediate vasodilator responses to BK in the rat heart but suggest a major role for a P450-dependent mechanism via AA metabolism.

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Selected References

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  1. Baydoun A. R., Woodward B. Effects of bradykinin in the rat isolated perfused heart: role of kinin receptors and endothelium-derived relaxing factor. Br J Pharmacol. 1991 Jul;103(3):1829–1833. doi: 10.1111/j.1476-5381.1991.tb09871.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bény J. L., Brunet P. C. Neither nitric oxide nor nitroglycerin accounts for all the characteristics of endothelially mediated vasodilatation of pig coronary arteries. Blood Vessels. 1988;25(6):308–311. [PubMed] [Google Scholar]
  3. Cachofeiro V., Nasjletti A. Increased vascular responsiveness to bradykinin in kidneys of spontaneously hypertensive rats. Effect of N omega-nitro-L-arginine. Hypertension. 1991 Nov;18(5):683–688. doi: 10.1161/01.hyp.18.5.683. [DOI] [PubMed] [Google Scholar]
  4. Flavahan N. A., Shimokawa H., Vanhoutte P. M. Pertussis toxin inhibits endothelium-dependent relaxations to certain agonists in porcine coronary arteries. J Physiol. 1989 Jan;408:549–560. doi: 10.1113/jphysiol.1989.sp017475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fulton D., McGiff J. C., Quilley J. Contribution of NO and cytochrome P450 to the vasodilator effect of bradykinin in the rat kidney. Br J Pharmacol. 1992 Nov;107(3):722–725. doi: 10.1111/j.1476-5381.1992.tb14513.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kontos H. A., Wei E. P., Povlishock J. T., Christman C. W. Oxygen radicals mediate the cerebral arteriolar dilation from arachidonate and bradykinin in cats. Circ Res. 1984 Sep;55(3):295–303. doi: 10.1161/01.res.55.3.295. [DOI] [PubMed] [Google Scholar]
  7. Messina E. J., Weiner R., Kaley G. Inhibition of bradykinin vasodilation and potentiation of norepinephrine and angiotensin vasoconstriction by inhibitors of prostaglandin synthesis in skeletal muscle of the rat. Circ Res. 1975 Oct;37(4):430–437. doi: 10.1161/01.res.37.4.430. [DOI] [PubMed] [Google Scholar]
  8. Oyekan A. O., McGiff J. C., Quilley J. Cytochrome P-450-dependent vasodilator responses to arachidonic acid in the isolated, perfused kidney of the rat. Circ Res. 1991 Apr;68(4):958–965. doi: 10.1161/01.res.68.4.958. [DOI] [PubMed] [Google Scholar]
  9. Oyekan A. O., McGiff J. C., Rosencrantz-Weiss P., Quilley J. Relaxant responses of rabbit aorta: influence of cytochrome P450 inhibitors. J Pharmacol Exp Ther. 1994 Jan;268(1):262–269. [PubMed] [Google Scholar]
  10. Pinto A., Abraham N. G., Mullane K. M. Arachidonic acid-induced endothelial-dependent relaxations of canine coronary arteries: contribution of a cytochrome P-450-dependent pathway. J Pharmacol Exp Ther. 1987 Mar;240(3):856–863. [PubMed] [Google Scholar]
  11. Richard V., Tanner F. C., Tschudi M., Lüscher T. F. Different activation of L-arginine pathway by bradykinin, serotonin, and clonidine in coronary arteries. Am J Physiol. 1990 Nov;259(5 Pt 2):H1433–H1439. doi: 10.1152/ajpheart.1990.259.5.H1433. [DOI] [PubMed] [Google Scholar]
  12. Tschudi M., Richard V., Bühler F. R., Lüscher T. F. Importance of endothelium-derived nitric oxide in porcine coronary resistance arteries. Am J Physiol. 1991 Jan;260(1 Pt 2):H13–H20. doi: 10.1152/ajpheart.1991.260.1.H13. [DOI] [PubMed] [Google Scholar]
  13. Vane J. R., Anggård E. E., Botting R. M. Regulatory functions of the vascular endothelium. N Engl J Med. 1990 Jul 5;323(1):27–36. doi: 10.1056/NEJM199007053230106. [DOI] [PubMed] [Google Scholar]
  14. Zou A. P., Imig J. D., Kaldunski M., Ortiz de Montellano P. R., Sui Z., Roman R. J. Inhibition of renal vascular 20-HETE production impairs autoregulation of renal blood flow. Am J Physiol. 1994 Feb;266(2 Pt 2):F275–F282. doi: 10.1152/ajprenal.1994.266.2.F275. [DOI] [PubMed] [Google Scholar]
  15. Zou A. P., Ma Y. H., Sui Z. H., Ortiz de Montellano P. R., Clark J. E., Masters B. S., Roman R. J. Effects of 17-octadecynoic acid, a suicide-substrate inhibitor of cytochrome P450 fatty acid omega-hydroxylase, on renal function in rats. J Pharmacol Exp Ther. 1994 Jan;268(1):474–481. [PubMed] [Google Scholar]

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