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Celiprolol has no direct or indirect relaxing effects in isolated arteries and veins
1Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota.
Insights
Celiprolol did not directly relax isolated blood vessels. However, it acted as a beta-adrenoceptor antagonist in coronary arteries, indicating its vascular effects are not due to direct vasodilation.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- Celiprolol is a beta-blocker with potential vasodilatory properties.
- Understanding the mechanisms of drug-induced vasodilation is crucial for cardiovascular therapeutics.
Purpose of the Study:
- To investigate the direct and indirect mechanisms of celiprolol's potential vasodilator effect on isolated blood vessels.
- To determine if celiprolol interacts with endothelial function or adrenergic signaling.
Main Methods:
- Isometric tension recording in canine coronary artery and rat mesenteric artery rings.
- Assessment of relaxation responses to celiprolol, acetylcholine, isoproterenol, and papaverine.
- Measurement of [3H]norepinephrine overflow in canine saphenous vein strips to evaluate adrenergic neurotransmission.
Main Results:
- Celiprolol did not induce relaxation in isolated blood vessels, with or without endothelium.
- Celiprolol competitively inhibited isoproterenol-induced relaxation in canine coronary arteries, demonstrating beta-adrenoceptor antagonism.
- Celiprolol did not affect isoproterenol-augmented [3H]norepinephrine release from canine saphenous veins.
Conclusions:
- Celiprolol exhibits postjunctional beta-adrenoceptor antagonist activity in the coronary artery.
- No direct or indirect vasodilator effects of celiprolol were observed on isolated canine or rat blood vessels.
- The vasodilatory effects of celiprolol, if any, are likely mediated through mechanisms other than direct action on vascular smooth muscle or endothelium.
Abstract:
Experiments were designed to study the potential mechanisms underlying the vasodilator effect of celiprolol. Rings of canine left circumflex coronary artery and rat mesenteric artery, with and without endothelium, were suspended in organ chambers for isometric tension recording. In both blood vessels, celiprolol (10(-9)-10(-4) M) failed to produce relaxation in rings with and without endothelium; these same tissues relaxed in an endothelium-dependent manner to acetylcholine (10(-6) M). All tissues relaxed completely in the presence of papaverine (10(-4) M). In the coronary artery, isoproterenol (10(-9)-10(-4) M) produced endothelium-independent relaxations which were inhibited in a competitive fashion by celiprolol (pA2 = 7.52 +/- 0.14; slope = 0.98, 95% confidence limits = 0.80-1.15). In other experiments, strips of canine saphenous veins were incubated with [3H]norepinephrine [( 3H]NE) and suspended for superfusion. Electrical stimulation (2 Hz, 4 V, 2 ms for 6 min) produced an increase in [3H]NE overflow. Isoproterenol (2 X 10(-6) M) augmented the evoked release of [3H]NE. Treatment of the strips with celiprolol (up to 5 X 10(-6) M) did not inhibit isoproterenol-induced facilitation of [3H]NE release. Thus, although celiprolol is a potent antagonist of postjunctional beta-adrenoceptors in the coronary artery, no evidence was obtained for a direct or indirect vasodilator effect of celiprolol on isolated blood vessels.