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EFFECT OF TOLERANCE TO GLYCERYL TRINITRATE ON VASCULAR RESPONSES IN CONSCIOUS RABBITS
Author(s) -
Du Z. Y.,
Dusting G. J.,
Woodman O. L.
Publication year - 1991
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1991.tb01476.x
Subject(s) - phenylephrine , sodium nitroprusside , vasodilation , vasoconstriction , pharmacology , acetylcholine , vascular resistance , agonist , thromboxane a2 , chemistry , medicine , nitric oxide , anesthesia , blood pressure , receptor
SUMMARY 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 μg/kg per min intravenously (i.v.)), sodium nitroprusside (SNP, 5–20 μg/kg per min i.v.) and acetylcholine (ACh, 3–12 μg/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 α 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 α 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 α 1 ‐ but not α 2 ‐adrenoceptor‐mediated vasoconstriction.