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Modification of the pressor effect of sympathomimetic drugs by carvedilol: the role of nitric oxide and propranolol
Author(s) -
Simaan Joseph A.,
Hitti Lourdes
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1128.5
Subject(s) - nitric oxide , propranolol , chemistry , tyramine , vasodilation , norepinephrine , endocrinology , medicine , pharmacology , biochemistry , organic chemistry , dopamine
The pressor effect of single intravenous doses of norepinephrine (NE 0.05, 0.1, 0.2 ug) and tyramine (T 0.025, 0.5, 0.1 mg) was assessed in anesthetized Sprague‐Dawley rats under pentobarbital anesthesia by measuring systolic carotid pressure before and after carvedilol (C), a beta‐ and alpha1‐adrenoceptor blocker with arteriolar dilating action, given in cumulative doses to produce maximal changes. C (1.36±0.1 mg/kg N=8) reduced the pressor effect of NE and T in all doses by 15–36% and 33–41% respectively that was prevented by subsequent blockade of nitric oxide synthesis with nitro‐L‐arginine (NA 15 mg/kg) and restoration of the basal level of nitric oxide with nitroglycerin (NG) a nitric oxide donor, without further change after propranolol (P 1 mg/kg). The effect of C was also prevented after P (N=9) by 8–27% and 32–42% respectively. NA‐NG was without further effect. C given after P (N=10) potentiated the pressor effect of NE and T by 44–59% and 17–41% respectively without change after NA‐NG. C enhanced the depressor effect of acetylcholine (AC 0.1–0.5 ug) by 15–32% (N=8) which was prevented by NA‐NG. It is concluded that C enhances the synthesis of nitric oxide which decreases the pressor effect of NE and T and enhances the depressor effect of AC and that this effect is counteracted by blocking nitric oxide synthesis and by P. The link between C and P and the nitric oxide pathway needs further exploration. Supported by AUB.