Abstract
1. Male, Long Evans rats (350-450 g) were chronically instrumented to allow monitoring of mean arterial blood pressure, heart rate and changes in renal, mesenteric and hindquarters haemodynamics. In the first experiment, animals (n = 8) were given a bolus i.v. injection of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine hydrochloride (L-NMMA; 30 mg kg-1) on four consecutive days. Fifteen min prior to L-NMMA administration on the fourth day, the endothelin, ETA-, ETB-receptor antagonist, bosentan, was injected (30 mg kg-1, i.v.). Relative to the response on the third day, bosentan caused 33 +/- 4%, 24 +/- 3%, 14 +/- 3%, and 18 +/- 5% inhibition of the pressor, and renal, mesenteric and hindquarters vasoconstrictor effects of L-NMMA, respectively. 2. In the second experiment, bosentan was given 15 min before L-NMMA in a group of rats (n = 6) which had not received L-NMMA previously. Relative to the responses to L-NMMA on the first day in the previous experiment, bosentan caused a 30%, 24%, 18% and 27% inhibition of the pressor, and renal, mesenteric and hindquarters vasoconstrictor effects of L-NMMA, respectively. 3. The results indicate a significant contribution from endothelin to the haemodynamic effects of L-NMMA in conscious rats. However, since our previous studies have shown the renin-angiotensin and sympathoadrenal systems are not involved, it is likely that the major component of the cardiovascular response to L-NMMA in conscious rats is due to loss of vasodilator action of endothelial nitric oxide.
Full text
PDF


Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boulanger C., Lüscher T. F. Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. J Clin Invest. 1990 Feb;85(2):587–590. doi: 10.1172/JCI114477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clozel M., Breu V., Gray G. A., Kalina B., Löffler B. M., Burri K., Cassal J. M., Hirth G., Müller M., Neidhart W. Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist. J Pharmacol Exp Ther. 1994 Jul;270(1):228–235. [PubMed] [Google Scholar]
- Gardiner S. M., Compton A. M., Bennett T., Palmer R. M., Moncada S. Control of regional blood flow by endothelium-derived nitric oxide. Hypertension. 1990 May;15(5):486–492. doi: 10.1161/01.hyp.15.5.486. [DOI] [PubMed] [Google Scholar]
- Gardiner S. M., Compton A. M., Kemp P. A., Bennett T. Regional and cardiac haemodynamic effects of NG-nitro-L-arginine methyl ester in conscious, Long Evans rats. Br J Pharmacol. 1990 Nov;101(3):625–631. doi: 10.1111/j.1476-5381.1990.tb14131.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gardiner S. M., Compton A. M., Kemp P. A., Bennett T. Regional and cardiac haemodynamic responses to glyceryl trinitrate, acetylcholine, bradykinin and endothelin-1 in conscious rats: effects of NG-nitro-L-arginine methyl ester. Br J Pharmacol. 1990 Nov;101(3):632–639. doi: 10.1111/j.1476-5381.1990.tb14132.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gardiner S. M., Kemp P. A., March J. E., Bennett T., Davenport A. P., Edvinsson L. Effects of an ET1-receptor antagonist, FR139317, on regional haemodynamic responses to endothelin-1 and [Ala11,15]Ac-endothelin-1 (6-21) in conscious rats. Br J Pharmacol. 1994 Jun;112(2):477–486. doi: 10.1111/j.1476-5381.1994.tb13098.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gardiner S. M., Kemp P. A., March J. E., Bennett T. Effects of bosentan (Ro 47-0203), an ETA-, ETB-receptor antagonist, on regional haemodynamic responses to endothelins in conscious rats. Br J Pharmacol. 1994 Jul;112(3):823–830. doi: 10.1111/j.1476-5381.1994.tb13153.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lacolley P. J., Lewis S. J., Brody M. J. Role of sympathetic nerve activity in the generation of vascular nitric oxide in urethane-anesthetized rats. Hypertension. 1991 Jun;17(6 Pt 2):881–887. doi: 10.1161/01.hyp.17.6.881. [DOI] [PubMed] [Google Scholar]
- Richard V., Hogie M., Clozel M., Löffler B. M., Thuillez C. In vivo evidence of an endothelin-induced vasopressor tone after inhibition of nitric oxide synthesis in rats. Circulation. 1995 Feb 1;91(3):771–775. doi: 10.1161/01.cir.91.3.771. [DOI] [PubMed] [Google Scholar]
- Sigmon D. H., Carretero O. A., Beierwaltes W. H. Angiotensin dependence of endothelium-mediated renal hemodynamics. Hypertension. 1992 Nov;20(5):643–650. doi: 10.1161/01.hyp.20.5.643. [DOI] [PubMed] [Google Scholar]
- Thompson A., Valeri C. R., Lieberthal W. Endothelin receptor A blockade alters hemodynamic response to nitric oxide inhibition in rats. Am J Physiol. 1995 Aug;269(2 Pt 2):H743–H748. doi: 10.1152/ajpheart.1995.269.2.H743. [DOI] [PubMed] [Google Scholar]
- Vargas H. M., Ignarro L. J., Chaudhuri G. Physiological release of nitric oxide is dependent on the level of vascular tone. Eur J Pharmacol. 1990 Nov 13;190(3):393–397. doi: 10.1016/0014-2999(90)94204-b. [DOI] [PubMed] [Google Scholar]
- Widdop R. E., Gardiner S. M., Kemp P. A., Bennett T. The influence of atropine and atenolol on the cardiac haemodynamic effects of NG-nitro-L-arginine methyl ester in conscious, Long Evans rats. Br J Pharmacol. 1992 Mar;105(3):653–656. doi: 10.1111/j.1476-5381.1992.tb09034.x. [DOI] [PMC free article] [PubMed] [Google Scholar]