Direct Vasodilatation by Labetalol in Anaesthetized Dogs

Dage, Richard C.; Hsieh, Chih Peng

doi:10.1111/j.1476-5381.1980.tb07934.x

Cited by 27 publications

(15 citation statements)

References 15 publications

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“…Dage and Hsieh showed in anesthetized dogs that intraarterial labetalol caused a dose-related direct vasodilatation of resistance blood vessels similar to that seen with hydralazine [15]. Again, these effects were observed despite the presence of propranolol and phentolamine.…”

Section: Hemodynamic and Antihypertensive Effectsmentioning

confidence: 79%

“…Over the range of in vitro and in vivo tests used, labetalol has been shown to be 6 to 10 times less potent than phentolamine at a-adrenoceptors, 1.5 to 4 times less potent than propranolol at ~-adrenoceptors, and was itself 4 to 16 times less potent at a-than at 6-adrenoceptors [8]. The drug has also been shown to have partial ~2-agonist properties [10][11][12][13], as well as the ability to cause direct vasodilatation [10,14,15].…”

Section: Experimental Models and Clinical Pharmacologymentioning

confidence: 99%

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Properties of labetalol, a combined ?-and ?-blocking agent, relevant to the treatment of myocardial ischemia

Frishman

1988

Cardiovasc Drug Ther

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Labetalol, a combined alpha-beta-adrenergic antagonist, is one of the new group of beta-adrenergic blockers reduces peripheral and coronary vascular resistances while preserving cardiac output. Unlike alpha-adrenergic blockers, labetalol tends to reduce heart rate during rest and exercise. The drug is a potent antihypertensive agent which has been used by mouth and by vein to treat mild, moderate, and severe hypertension, including hypertensive emergencies. Labetalol has a hemodynamic profile which makes it an attractive agent for treating myocardial ischemia. The drug reduces blood pressure, left ventricular wall tension, heart rate, and contractility while preserving or even augmenting coronary blood flow. Studies with labetalol in hypertensive patients with angina have shown it to be more effective than placebo in reducing angina attacks and blood pressure while improving exercise tolerance. The drug appears to have antianginal and antihypertensive effects comparable to atenolol and propranolol. Side effects of treatment are observed and most are related to alpha- and beta-adrenergic blockade. Labetalol also appears to be effective for treatment of normotensive patients with angina and for silent myocardial ischemia. It has no apparent effects on serum lipids and lipoproteins. Labetalol appears to be a useful drug for treating the hypertensive heart and its many complications.

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Section: Hemodynamic and Antihypertensive Effectsmentioning

confidence: 79%

Section: Experimental Models and Clinical Pharmacologymentioning

confidence: 99%

Properties of labetalol, a combined ?-and ?-blocking agent, relevant to the treatment of myocardial ischemia

Frishman

1988

Cardiovasc Drug Ther

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“…Intra-arterial labetalol increased femoral arterial blood flow in the dog hindlimb by a mechanism which did not appear to involve alphal-receptor blockade, as shown by major differences between the effects of prazosin in innervated and denervated limbs, whereas there were smaller and insignificant differences in the case of labetalol. They do not support the idea of a "direct vasodilatory action" of labetalol, independent of beta-stimulation, as has been suggested [9,11]. Tadepalli and Novak [4] evaluated the cardiac stimulating qualities versus the peripheral vasodilation in their assessment of the beta-stimulating properties of labetalol.…”

Section: Vasodilation By Beta-adrenergic Receptor Stimulationmentioning

confidence: 92%

“…Several lines of evidence favor a role for direct vasodilation [9] and more specifically beta-adrenergic receptor stimulation in the mechanism of the vasodilation of labetalol. Intra-arterial labetalol increased femoral arterial blood flow in the dog hindlimb by a mechanism which did not appear to involve alphal-receptor blockade, as shown by major differences between the effects of prazosin in innervated and denervated limbs, whereas there were smaller and insignificant differences in the case of labetalol.…”

Section: Vasodilation By Beta-adrenergic Receptor Stimulationmentioning

confidence: 99%

Role of vasobilation in the antihypertensive and antianginal effects of labetalol: Implications for therapy of combined hypertension and angina

Opie

1988

Cardiovasc Drug Ther

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Beta-adrenergic blockade is established therapy in the management of both hypertension and angina pectoris. This review evaluates the use of combined alpha-adrenergic and beta-adrenergic blockade for these conditions, with reference to labetalol. There are three major differences between labetalol and propranolol or similar conventional beta-blockers. First, in the mechanism of the antihypertensive effect, peripheral vasodilation plays a prominent role during the use of labetalol. In particular, acute therapy with labetalol rapidly reduces the blood pressure because of this reduction in the systemic vascular resistance. During prolonged therapy with labetalol over many years, blood pressure remains reduced with a sustained fall in the systemic vascular resistance. Second, in patients with combined hypertension and angina pectoris, fixed doses of labetalol (200 mg twice daily) gave the same blood pressure values, effort tolerance, and nitrate usage as did atenolol 100 mg once daily in a double-blind, double-dummy, crossover study. Labetalol gave higher heart rates at rest and during exercise (both p less than 0.01). The higher heart rate with labetalol could be an advantage in some patients with effort angina and a disadvantage in others. Third, in hypertensive asthmatics, labetalol appears to have a relative bronchosparing effect, when compared with propranolol. The possession by labetalol of beta2-stimulating qualities (intrinsic sympathomimetic activity) may explain part of the dilating effect and the bronchosparing quality. Thus labetalol 1) lowers blood pressure by a mechanism involving vasodilation, 2) has an equiantianginal effect to atenolol yet a higher heart rate, and 3) may be bronchosparing. Differences among various beta-blockers may be important in matching the properties of the beta-blocker chosen to the requirements of the individual patient.

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“…Like prazosin, labetalol appears to inhibit selectively a1-(postsynaptic, vascular) adrenoceptors rather than a2-(presynaptic) adrenoceptors, responsible for negative feedback control of neurotransmitter release (Levy & Richards, 1980;Hoffman & Lefkowitz, 1980). Though labetalol is a more potent inhibitor of I-than a-adrenergic receptors (Mehta & Cohen, 1977), the drug possesses partial ,32-adrenoceptor agonist properties and also displays direct vasodilator effects (Baum & Sybertz, 1983;Dage & Hsieh, 1980). Propranolol, by blocking both l-and 12-adrenoceptors, lowers heart rate, blood pressure and cardiac output and exerts a constrictor effect upon peripheral arterioles and veins (Ahlquist, 1965;Smith & Warren, 1982a,b).…”

Section: Discussionmentioning

confidence: 99%

Effect of labetalol on limb haemodynamics in patients following coronary artery bypass graft surgery.

Halperin¹,

Mindich²,

Rothlauf³

et al. 1986

Brit J Clinical Pharma

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Labetalol is a competitive inhibitor of alpha‐ and beta‐adrenergic receptors and has an antihypertensive action. To determine limb haemodynamic effects, we measured calf blood flow and venous capacitance by venous occlusion plethysmography before and after oral labetalol in 10 patients 3‐7 days following coronary bypass surgery. Vascular resistance was calculated as the ratio of mean arterial pressure to arterial flow. The peak effect of labetalol was taken as the point of maximum blood pressure decline, and this interval was selected for evaluation of the limb haemodynamic response. Ninety to 120 min after administration of 100‐200 mg of labetalol the mean blood pressure fell from 88 +/‐ 3 to 79 +/‐ 3 mm Hg; (P less than 0.005). The mean arterial blood flow registered 5.1 +/‐ 1.0 ml 100 ml‐1 limb tissue min‐1 which was not significantly different from the control value of 4.4 +/‐ 0.8 ml 100 ml‐1 limb tissue min‐1. The calculated index of limb vascular resistance was not affected by labetalol administration, averaging 37 +/‐ 12 mm Hg 100‐1 ml limb tissue min‐1 before labetalol and 30 +/‐ 11 mm Hg ml‐1 100 ml limb tissue min‐1 at the time of peak hypotensive effect. There was a slight but statistically significant increment in limb venous volume to 1.9 +/‐ 0.3 from 1.5 +/‐ 0.3 ml 100 ml‐1 limb tissue (P less than 0.025). Placebo administration produced no consistent changes in blood pressure, arterial blood flow, vascular resistance or venous capacitance.(ABSTRACT TRUNCATED AT 250 WORDS)

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Direct Vasodilatation by Labetalol in Anaesthetized Dogs

Cited by 27 publications

References 15 publications

Properties of labetalol, a combined ?-and ?-blocking agent, relevant to the treatment of myocardial ischemia

Properties of labetalol, a combined ?-and ?-blocking agent, relevant to the treatment of myocardial ischemia

Role of vasobilation in the antihypertensive and antianginal effects of labetalol: Implications for therapy of combined hypertension and angina

Effect of labetalol on limb haemodynamics in patients following coronary artery bypass graft surgery.

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