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Effect of tolerance to glyceryl trinitrate on vascular responses in conscious rabbits.
Effect of tolerance to glyceryl trinitrate on vascular responses in conscious rabbits.
- Source :
-
Clinical and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] 1991 Jun; Vol. 18 (6), pp. 439-47. - Publication Year :
- 1991
-
Abstract
- 1. The effect of tolerance to glyceryl trinitrate (GTN) on vasodilator and vasoconstrictor responses was examined in conscious rabbits and isolated rabbit aortic rings. 2. In conscious rabbits, depressor responses to 5 min infusions of GTN (10-40 micrograms/kg per min intravenously (i.v.)), sodium nitroprusside (SNP, 5-20 micrograms/kg per min i.v.) and acetylcholine (ACh, 3-12 micrograms/kg per min i.v.) were examined before and after transdermal treatment with GTN (20 mg/48 h). GTN pretreatment significantly attenuated GTN-induced depressor responses, indicating the development of tolerance, but did not affect the reductions in arterial pressure induced by SNP or ACh. 3. Similarly, aortic rings taken from GTN pretreated rabbits exhibited tolerance to GTN but the relaxant responses to SNP or the calcium ionophore A23187 were not affected. In the aortic rings from GTN-tolerant rabbits contractile responses to serotonin or the thromboxane-mimetic U46619 were significantly attenuated, in contrast to the responses to the alpha 1-adrenoceptor agonist phenylephrine (PE) which were significantly enhanced. 4. Similarly, in conscious rabbits, PE-induced increases in arterial pressure and hindlimb vascular resistance were significantly enhanced by GTN pretreatment but the responses to the alpha 2-adrenoceptor agonist BHT 920 were unaffected. 5. In conclusion, tolerance to GTN does not affect endothelium-dependent vasodilatation but does cause a selective enhancement of alpha 1- but not alpha 2-adrenoceptor-mediated vasoconstriction.
- Subjects :
- Administration, Cutaneous
Animals
Aorta, Thoracic physiology
Consciousness
Drug Tolerance physiology
Endothelium, Vascular physiology
Female
Hemodynamics drug effects
Male
Muscle Contraction drug effects
Muscle Relaxation drug effects
Rabbits
Vasoconstrictor Agents pharmacology
Aorta, Thoracic drug effects
Endothelium, Vascular drug effects
Nitroglycerin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0305-1870
- Volume :
- 18
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Clinical and experimental pharmacology & physiology
- Publication Type :
- Academic Journal
- Accession number :
- 1914247
- Full Text :
- https://doi.org/10.1111/j.1440-1681.1991.tb01476.x