Abstract
1. Angiotensin converting enzyme (ACE) inhibition has been shown to restore the impaired endothelial function in hypertension, but the mediators underlying the promoted endothelium-dependent dilatation have not been fully characterized. Therefore, we investigated the effects of 10-week-long quinapril therapy (10 mg kg-1 day-1) on responses of mesenteric arterial rings in vitro from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Endothelium-dependent relaxations of noradrenaline (NA)-precontracted rings to acetylcholine (ACh) and adenosine 5'-diphosphate (ADP) were similar in WKY rats and quinapril-treated SHR and more pronounced than in untreated SHR. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) attenuated the relaxations in both WKY groups and quinapril-treated SHR, and completely inhibited them in untreated SHR. When endothelium-dependent hyperpolarization was prevented by precontraction of the preparations with potassium chloride (KCl), no differences were found in relaxations to ACh and ADP between the study groups. In addition, in NA-precontracted rings the L-NAME- and indomethacin-resistant relaxations to ACh were partially prevented by apamin, an inhibitor of calcium-activated potassium channels. 3. Interestingly, in quinapril-treated SHR but not in the other groups, exogenous bradykinin potentiated the relaxations to ACh in both NA- and KCl-precontracted arterial rings. 4. Contractile sensitivity of endothelium-intact rings to NA was reduced in SHR by quinapril, and was more effectively increased by L-NAME in quinapril-treated than untreated SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Full text
PDF








Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adeagbo A. S., Triggle C. R. Varying extracellular [K+]: a functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed. J Cardiovasc Pharmacol. 1993 Mar;21(3):423–429. [PubMed] [Google Scholar]
- Arvola P., Pörsti I., Vuorinen P., Pekki A., Vapaatalo H. Contractions induced by potassium-free solution and potassium relaxation in vascular smooth muscle of hypertensive and normotensive rats. Br J Pharmacol. 1992 May;106(1):157–165. doi: 10.1111/j.1476-5381.1992.tb14309.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arvola P., Ruskoaho H., Wuorela H., Pekki A., Vapaatalo H., Pörsti I. Quinapril treatment and arterial smooth muscle responses in spontaneously hypertensive rats. Br J Pharmacol. 1993 Apr;108(4):980–990. doi: 10.1111/j.1476-5381.1993.tb13495.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Auch-Schwelk W., Bossaller C., Claus M., Graf K., Gräfe M., Fleck E. ACE inhibitors are endothelium dependent vasodilators of coronary arteries during submaximal stimulation with bradykinin. Cardiovasc Res. 1993 Feb;27(2):312–317. doi: 10.1093/cvr/27.2.312. [DOI] [PubMed] [Google Scholar]
- Auch-Schwelk W., Bossaller C., Claus M., Graf K., Gräfe M., Fleck E. Local potentiation of bradykinin-induced vasodilation by converting-enzyme inhibition in isolated coronary arteries. J Cardiovasc Pharmacol. 1992;20 (Suppl 9):S62–S67. [PubMed] [Google Scholar]
- Auch-Schwelk W., Katusić Z. S., Vanhoutte P. M. Nitric oxide inactivates endothelium-derived contracting factor in the rat aorta. Hypertension. 1992 May;19(5):442–445. doi: 10.1161/01.hyp.19.5.442. [DOI] [PubMed] [Google Scholar]
- Baudin B., Drouet L. In vitro interactions between ramiprilat and angiotensin I-converting enzyme in endothelial cells. J Cardiovasc Pharmacol. 1989;14 (Suppl 4):S37–S42. [PubMed] [Google Scholar]
- Bossaller C., Auch-Schwelk W., Weber F., Götze S., Gräfe M., Graf K., Fleck E. Endothelium-dependent relaxations are augmented in rats chronically treated with the angiotensin-converting enzyme inhibitor enalapril. J Cardiovasc Pharmacol. 1992;20 (Suppl 9):S91–S95. [PubMed] [Google Scholar]
- Bray K., Quast U. Differences in the K(+)-channels opened by cromakalim, acetylcholine and substance P in rat aorta and porcine coronary artery. Br J Pharmacol. 1991 Mar;102(3):585–594. doi: 10.1111/j.1476-5381.1991.tb12217.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen G., Suzuki H., Weston A. H. Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol. 1988 Dec;95(4):1165–1174. doi: 10.1111/j.1476-5381.1988.tb11752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clozel M., Kuhn H., Hefti F. Effects of angiotensin converting enzyme inhibitors and of hydralazine on endothelial function in hypertensive rats. Hypertension. 1990 Nov;16(5):532–540. doi: 10.1161/01.hyp.16.5.532. [DOI] [PubMed] [Google Scholar]
- Cocks T. M., Angus J. A. Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature. 1983 Oct 13;305(5935):627–630. doi: 10.1038/305627a0. [DOI] [PubMed] [Google Scholar]
- Fasciolo J. C., Vargas L., Lama M. C., Nolly H. Bradykinin-induced vasoconstriction of rat mesenteric arteries precontracted with noradrenaline. Br J Pharmacol. 1990 Oct;101(2):344–348. doi: 10.1111/j.1476-5381.1990.tb12712.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feletou M., Vanhoutte P. M. Endothelium-dependent hyperpolarization of canine coronary smooth muscle. Br J Pharmacol. 1988 Mar;93(3):515–524. doi: 10.1111/j.1476-5381.1988.tb10306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujii K., Ohmori S., Tominaga M., Abe I., Takata Y., Ohya Y., Kobayashi K., Fujishima M. Age-related changes in endothelium-dependent hyperpolarization in the rat mesenteric artery. Am J Physiol. 1993 Aug;265(2 Pt 2):H509–H516. doi: 10.1152/ajpheart.1993.265.2.H509. [DOI] [PubMed] [Google Scholar]
- Fujii K., Tominaga M., Ohmori S., Kobayashi K., Koga T., Takata Y., Fujishima M. Decreased endothelium-dependent hyperpolarization to acetylcholine in smooth muscle of the mesenteric artery of spontaneously hypertensive rats. Circ Res. 1992 Apr;70(4):660–669. doi: 10.1161/01.res.70.4.660. [DOI] [PubMed] [Google Scholar]
- Garland C. J., McPherson G. A. Evidence that nitric oxide does not mediate the hyperpolarization and relaxation to acetylcholine in the rat small mesenteric artery. Br J Pharmacol. 1992 Feb;105(2):429–435. doi: 10.1111/j.1476-5381.1992.tb14270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gohlke P., Lamberty V., Kuwer I., Bartenbach S., Schnell A., Linz W., Schölkens B. A., Wiemer G., Unger T. Long-term low-dose angiotensin converting enzyme inhibitor treatment increases vascular cyclic guanosine 3',5'-monophosphate. Hypertension. 1993 Nov;22(5):682–687. doi: 10.1161/01.hyp.22.5.682. [DOI] [PubMed] [Google Scholar]
- Hecker M., Pörsti I., Bara A. T., Busse R. Potentiation by ACE inhibitors of the dilator response to bradykinin in the coronary microcirculation: interaction at the receptor level. Br J Pharmacol. 1994 Jan;111(1):238–244. doi: 10.1111/j.1476-5381.1994.tb14050.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ito S., Carretero O. A. Impaired response to acetylcholine despite intact endothelium-derived relaxing factor/nitric oxide in isolated microperfused afferent arterioles of the spontaneously hypertensive rat. J Cardiovasc Pharmacol. 1992;20 (Suppl 12):S187–S189. doi: 10.1097/00005344-199204002-00052. [DOI] [PubMed] [Google Scholar]
- Iwama Y., Kato T., Muramatsu M., Asano H., Shimizu K., Toki Y., Miyazaki Y., Okumura K., Hashimoto H., Ito T. Correlation with blood pressure of the acetylcholine-induced endothelium-derived contracting factor in the rat aorta. Hypertension. 1992 Apr;19(4):326–332. doi: 10.1161/01.hyp.19.4.326. [DOI] [PubMed] [Google Scholar]
- Jameson M., Dai F. X., Lüscher T., Skopec J., Diederich A., Diederich D. Endothelium-derived contracting factors in resistance arteries of young spontaneously hypertensive rats before development of overt hypertension. Hypertension. 1993 Mar;21(3):280–288. doi: 10.1161/01.hyp.21.3.280. [DOI] [PubMed] [Google Scholar]
- Kaplan H. R., Cohen D. M., Essenburg A. D., Major T. C., Mertz T. E., Ryan M. J. CI-906 and CI-907: new orally active nonsulfhydryl angiotensin-converting enzyme inhibitors. Fed Proc. 1984 Apr;43(5):1326–1329. [PubMed] [Google Scholar]
- Kelm M., Feelisch M., Krebber T., Motz W., Strauer B. E. The role of nitric oxide in the regulation of coronary vascular resistance in arterial hypertension: comparison of normotensive and spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1992;20 (Suppl 12):S183–S186. doi: 10.1097/00005344-199204002-00051. [DOI] [PubMed] [Google Scholar]
- Kähönen M., Arvola P., Wu X., Pörsti I. Arterial contractions induced by cumulative addition of calcium in hypertensive and normotensive rats: influence of endothelium. Naunyn Schmiedebergs Arch Pharmacol. 1994 Jun;349(6):627–636. doi: 10.1007/BF01258469. [DOI] [PubMed] [Google Scholar]
- Lee R. M., Berecek K. H., Tsoporis J., McKenzie R., Triggle C. R. Prevention of hypertension and vascular changes by captopril treatment. Hypertension. 1991 Feb;17(2):141–150. doi: 10.1161/01.hyp.17.2.141. [DOI] [PubMed] [Google Scholar]
- Levy B. I., Benessiano J., Poitevin P., Safar M. E. Endothelium-dependent mechanical properties of the carotid artery in WKY and SHR. Role of angiotensin converting enzyme inhibition. Circ Res. 1990 Feb;66(2):321–328. doi: 10.1161/01.res.66.2.321. [DOI] [PubMed] [Google Scholar]
- Li J., Bian K. A., Bukoski R. D. A non-cyclo-oxygenase, non-nitric oxide relaxing factor is present in resistance arteries of normotensive but not spontaneously hypertensive rats. Am J Med Sci. 1994 Jan;307(1):7–14. doi: 10.1097/00000441-199401000-00002. [DOI] [PubMed] [Google Scholar]
- Li J., Bukoski R. D. Endothelium-dependent relaxation of hypertensive resistance arteries is not impaired under all conditions. Circ Res. 1993 Feb;72(2):290–296. doi: 10.1161/01.res.72.2.290. [DOI] [PubMed] [Google Scholar]
- Lüscher T. F., Vanhoutte P. M. Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension. 1986 Apr;8(4):344–348. doi: 10.1161/01.hyp.8.4.344. [DOI] [PubMed] [Google Scholar]
- Major T. C., Overhiser R. W., Taylor D. G., Jr, Panek R. L. Effects of quinapril, a new angiotensin-converting enzyme inhibitor, on vasoconstrictor activity in the isolated, perfused mesenteric vasculature of hypertensive rats. J Pharmacol Exp Ther. 1993 Apr;265(1):187–193. [PubMed] [Google Scholar]
- Mombouli J. V., Illiano S., Nagao T., Scott-Burden T., Vanhoutte P. M. Potentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factors. Circ Res. 1992 Jul;71(1):137–144. doi: 10.1161/01.res.71.1.137. [DOI] [PubMed] [Google Scholar]
- Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
- Nakamura M., Funakoshi T., Yoshida H., Arakawa N., Suzuki T., Hiramori K. Endothelium-dependent vasodilation is augmented by angiotensin converting enzyme inhibitors in healthy volunteers. J Cardiovasc Pharmacol. 1992 Dec;20(6):949–954. doi: 10.1097/00005344-199212000-00015. [DOI] [PubMed] [Google Scholar]
- Rubanyi G. M., Kauser K., Gräser T. Effect of cilazapril and indomethacin on endothelial dysfunction in the aortas of spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1993;22 (Suppl 5):S23–S30. doi: 10.1097/00005344-199322005-00005. [DOI] [PubMed] [Google Scholar]
- Takase H., Dohi Y., Kojima M., Sato K. Changes in the endothelial cyclooxygenase pathway in resistance arteries of spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1994 Feb;23(2):326–330. [PubMed] [Google Scholar]
- Tesfamariam B., Halpern W. Endothelium-dependent and endothelium-independent vasodilation in resistance arteries from hypertensive rats. Hypertension. 1988 May;11(5):440–444. doi: 10.1161/01.hyp.11.5.440. [DOI] [PubMed] [Google Scholar]
- Treasure C. B., Manoukian S. V., Klein J. L., Vita J. A., Nabel E. G., Renwick G. H., Selwyn A. P., Alexander R. W., Ganz P. Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients. Circ Res. 1992 Oct;71(4):776–781. doi: 10.1161/01.res.71.4.776. [DOI] [PubMed] [Google Scholar]
- Vanheel B., Van de Voorde J., Leusen I. Contribution of nitric oxide to the endothelium-dependent hyperpolarization in rat aorta. J Physiol. 1994 Mar 1;475(2):277–284. doi: 10.1113/jphysiol.1994.sp020068. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watt P. A., Thurston H. Endothelium-dependent relaxation in resistance vessels from the spontaneously hypertensive rats. J Hypertens. 1989 Aug;7(8):661–666. doi: 10.1097/00004872-198908000-00010. [DOI] [PubMed] [Google Scholar]
- Wiemer G., Schölkens B. A., Becker R. H., Busse R. Ramiprilat enhances endothelial autacoid formation by inhibiting breakdown of endothelium-derived bradykinin. Hypertension. 1991 Oct;18(4):558–563. doi: 10.1161/01.hyp.18.4.558. [DOI] [PubMed] [Google Scholar]
