Effects of α2-adrenergic stimulation with UK 14,304-18 on the heart and peripheral circulation of intact dogs

Stephen Algeo, Christopher P. Appleton, Gary V. Martin, Richard W. Lee, Rosel Mulkey, Marcey Olajos, Steven Goldman

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Abstract

To determine the extent of α2-adrenoreceptor control of cardiovascular function, we studied the hemodynamic effects of the relatively selective α2-adrenergic agonist UK 14,304-18 on the heart and peripheral circulation of intact dogs. Administration of increasing intravenous doses of UK 14,304-18 to conscious dogs given atropine to maintain heart rate (HR) resulted in a reproducible increase in mean aortic (AO) pressure (77.6 ± 5.0 to 136.4 ± 6.5 mm Hg, p < 0.05) and reductions in stroke volume (31.7 ± 2.9 to 17.9 ± 1.9 ml/kg/min, p < 0.05) and left ventricular (LV) dP/dt (2,120 ± 280.0 to 1,463 ± 196.1 mm Hg/s, p < 0.05). In ganglion-blocked dogs UK 14,304-18 did not alter the slope of the LV endsystolic pressure-volume relationship when compared with angiotensin and nitroprusside (79.9 ± 11.1 control vs. 73.3 ± 8.7 mm Hg/ml/kg UK 14,304-18, p > 0.05), nor did it change the volume intercept (-0.46 ± 0.12 control vs. -0.53 ± 0.16 ml/kg UK 14,304-18, p > 0.05) indicating no direct effect on LV contractile function. Changes in indices of diastolic function, including the time constant of isovolumic relaxation, time to peak filling, and chamber volume elasticity were similar to those of equipressor doses of angiotensin, indicating no direct effect on LV diastolic function. Effects on the peripheral circulation were studied in dogs undergoing transient acetylcholine-induced circulatory arrest. UK 14,304-18 increased mean circulatory filling pressure (7.9 ± 0.3 to 10.3 ± 0.2 mm Hg, p < 0.05) and the pressure gradient for venous return (7.6 ± 0.4 to 9.0 ± 0.3 mm Hg, p < 0.05). Central blood volume increased with UK 14,304-18 (15.6 ± 1.1 to 18.7 ± 1.5 ml/kg, p < 0.05), but this increase was not sufficient to maintain cardiac output (CO) during the UK 14,304-18 infusion, which decreased from 157.4 ± 11.1 to 131.5 ± 8.9 ml/kg/min (p < 0.01) in the presence of increased LV afterload. The time constant of relaxation of the arterial system increased and the arterial compliance decreased with increasing mean arterial pressure. Thus, this relatively selective α2 agonist does not directly alter cardiac function but increases tone in arterial resistance vessels and in systemic veins. The fall in CO appears to be caused by a mismatch between preload and afterload, which is the net result of quantitatively different effects on systemic veins and arteries.

Original languageEnglish (US)
Pages (from-to)1055-1064
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume7
Issue number6
DOIs
StatePublished - Jan 1 1985

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Keywords

  • Hemodynamics in dogs
  • Peripheral circulation
  • UK 14,304-18
  • Ventricular diastolic function
  • Ventricular systolic function
  • α-Adrenergic agonists

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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