Peripheral vascular effects of beta-3 adrenergic receptor stimulation in conscious dogs

Y. T. Shen, H. Zhang, Stephen Vatner

Research output: Contribution to journalArticle

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Abstract

To characterize the physiological function of the beta-3 adrenergic receptor subtype in vivo, the effects of a beta-3 adrenergic receptor agonist, BRL37344, were examined on systemic hemodynamics and regional blood flow distribution. They were compared with beta-1 or beta-2 adrenergic receptor stimulation using isoproterenol (ISO) in conscious dogs instrumented with aortic and left atrial catheters and ascending aortic flow probes. ISO, at a dose of 0.4 μg/kg/min i.v., reduced mean arterial pressure by 7 ± 3% and increased total peripheral conductance by 145 ± 12% and heart rate by 109 ± 10%. BRL37344, at a dose of 8.3 μg/kg i.v., reduced mean arterial pressure by 9 ± 4% and increased total peripheral conductance by 91 ± 3% and heart rate by 63 ± 5%. In the presence of selective beta-1 adrenergic receptor blockade with atenolol, ISO decreased mean arterial pressure by 20 ± 5% and increased total peripheral conductance by 140 ± 26% and heart rate by 60 ± 12%. After combined beta-1 and beta-2 adrenergic receptor blockade with propranolol, ISO induced no significant effects. By contrast, after propranolol, BRL37344 still reduced mean arterial pressure by 13 ± 2% and increased total peripheral conductance by 109 ± 8% and heart rate by 45 ± 5%. The beta-3 adrenergic receptor-mediated increase in total peripheral conductance (+146 ± 8%) persisted after combined blockades, i.e., beta and alpha adrenergic, cholinergic, histaminergic, purinergic, prostaglandin and endothelium-derived relaxing factor blockades. Studies that used radioactive microspheres demonstrated a different pattern of regional blood flow distribution with beta-3 adrenergic receptor stimulation compared with ISO- induced beta-1 and beta-2 adrenergic receptor-mediated peripheral vasodilation, i.e., BRL37344 increased blood flow preferentially to the skin (+570 ± 159%) and fat (+685 ± 195%) and the response was not affected by propranolol. Thus, in conscious dogs pretreated with propranolol, beta-3 adrenergic receptor stimulation induced sustained peripheral vasodilation, primarily in the skin and fat. The mechanism appears to be independent of generally recognized mediators of peripheral vasodilation.

Original languageEnglish (US)
Pages (from-to)466-473
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume268
Issue number1
StatePublished - Jan 1 1994

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Adrenergic beta-3 Receptors
Isoproterenol
Adrenergic beta-2 Receptors
Blood Vessels
Propranolol
Dogs
Arterial Pressure
Heart Rate
Vasodilation
Regional Blood Flow
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-1 Receptors
Fats
Endothelium-Dependent Relaxing Factors
Skin
Atenolol
Microspheres
Adrenergic Agents
Cholinergic Agents
Prostaglandins

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

@article{72d4bba7151141eab1fca991a2e915db,
title = "Peripheral vascular effects of beta-3 adrenergic receptor stimulation in conscious dogs",
abstract = "To characterize the physiological function of the beta-3 adrenergic receptor subtype in vivo, the effects of a beta-3 adrenergic receptor agonist, BRL37344, were examined on systemic hemodynamics and regional blood flow distribution. They were compared with beta-1 or beta-2 adrenergic receptor stimulation using isoproterenol (ISO) in conscious dogs instrumented with aortic and left atrial catheters and ascending aortic flow probes. ISO, at a dose of 0.4 μg/kg/min i.v., reduced mean arterial pressure by 7 ± 3{\%} and increased total peripheral conductance by 145 ± 12{\%} and heart rate by 109 ± 10{\%}. BRL37344, at a dose of 8.3 μg/kg i.v., reduced mean arterial pressure by 9 ± 4{\%} and increased total peripheral conductance by 91 ± 3{\%} and heart rate by 63 ± 5{\%}. In the presence of selective beta-1 adrenergic receptor blockade with atenolol, ISO decreased mean arterial pressure by 20 ± 5{\%} and increased total peripheral conductance by 140 ± 26{\%} and heart rate by 60 ± 12{\%}. After combined beta-1 and beta-2 adrenergic receptor blockade with propranolol, ISO induced no significant effects. By contrast, after propranolol, BRL37344 still reduced mean arterial pressure by 13 ± 2{\%} and increased total peripheral conductance by 109 ± 8{\%} and heart rate by 45 ± 5{\%}. The beta-3 adrenergic receptor-mediated increase in total peripheral conductance (+146 ± 8{\%}) persisted after combined blockades, i.e., beta and alpha adrenergic, cholinergic, histaminergic, purinergic, prostaglandin and endothelium-derived relaxing factor blockades. Studies that used radioactive microspheres demonstrated a different pattern of regional blood flow distribution with beta-3 adrenergic receptor stimulation compared with ISO- induced beta-1 and beta-2 adrenergic receptor-mediated peripheral vasodilation, i.e., BRL37344 increased blood flow preferentially to the skin (+570 ± 159{\%}) and fat (+685 ± 195{\%}) and the response was not affected by propranolol. Thus, in conscious dogs pretreated with propranolol, beta-3 adrenergic receptor stimulation induced sustained peripheral vasodilation, primarily in the skin and fat. The mechanism appears to be independent of generally recognized mediators of peripheral vasodilation.",
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Peripheral vascular effects of beta-3 adrenergic receptor stimulation in conscious dogs. / Shen, Y. T.; Zhang, H.; Vatner, Stephen.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 268, No. 1, 01.01.1994, p. 466-473.

Research output: Contribution to journalArticle

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N2 - To characterize the physiological function of the beta-3 adrenergic receptor subtype in vivo, the effects of a beta-3 adrenergic receptor agonist, BRL37344, were examined on systemic hemodynamics and regional blood flow distribution. They were compared with beta-1 or beta-2 adrenergic receptor stimulation using isoproterenol (ISO) in conscious dogs instrumented with aortic and left atrial catheters and ascending aortic flow probes. ISO, at a dose of 0.4 μg/kg/min i.v., reduced mean arterial pressure by 7 ± 3% and increased total peripheral conductance by 145 ± 12% and heart rate by 109 ± 10%. BRL37344, at a dose of 8.3 μg/kg i.v., reduced mean arterial pressure by 9 ± 4% and increased total peripheral conductance by 91 ± 3% and heart rate by 63 ± 5%. In the presence of selective beta-1 adrenergic receptor blockade with atenolol, ISO decreased mean arterial pressure by 20 ± 5% and increased total peripheral conductance by 140 ± 26% and heart rate by 60 ± 12%. After combined beta-1 and beta-2 adrenergic receptor blockade with propranolol, ISO induced no significant effects. By contrast, after propranolol, BRL37344 still reduced mean arterial pressure by 13 ± 2% and increased total peripheral conductance by 109 ± 8% and heart rate by 45 ± 5%. The beta-3 adrenergic receptor-mediated increase in total peripheral conductance (+146 ± 8%) persisted after combined blockades, i.e., beta and alpha adrenergic, cholinergic, histaminergic, purinergic, prostaglandin and endothelium-derived relaxing factor blockades. Studies that used radioactive microspheres demonstrated a different pattern of regional blood flow distribution with beta-3 adrenergic receptor stimulation compared with ISO- induced beta-1 and beta-2 adrenergic receptor-mediated peripheral vasodilation, i.e., BRL37344 increased blood flow preferentially to the skin (+570 ± 159%) and fat (+685 ± 195%) and the response was not affected by propranolol. Thus, in conscious dogs pretreated with propranolol, beta-3 adrenergic receptor stimulation induced sustained peripheral vasodilation, primarily in the skin and fat. The mechanism appears to be independent of generally recognized mediators of peripheral vasodilation.

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