Effects of alpha 2-adrenergic stimulation with UK 14,304-18 on the heart and peripheral circulation of intact dogs.
To determine the extent of alpha 2-adrenoreceptor control of cardiovascular function, we studied the hemodynamic effects of the relatively selective alpha 2-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 less than 0.05) and reductions in stroke volume (31.7 +/- 2.9 to 17.9 +/- 1.9 ml/kg/min, p less than 0.05) and left ventricular (LV) dP/dt (2,120 +/- 280.0 to 1,463 +/- 196.1 mm Hg/s, p less than 0.05). In ganglion-blocked dogs UK 14,304-18 did not alter the slope of the LV end-systolic 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 greater than 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 greater than 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 less than 0.05) and the pressure gradient for venous return (7.6 +/- 0.4 to 9.0 +/- 0.3 mm Hg, p less than 0.05). Central blood volume increased with UK 14,304-18 (15.6 +/- 1.1 to 18.7 +/- 1.5 ml/kg, p less than 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 less than 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 alpha 2 agonist does not directly alter cardiac function but increased 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.
S
S
Algeo
C P
CP
Appleton
G V
GV
Martin
R W
RW
Lee
R
R
Mulkey
M
M
Olajos
S
S
Goldman
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005730:Ganglionic Blockers / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D005730:Ganglionic Blockers; D011810:Quinoxalines; D015016:Yohimbine; D000068438:Brimonidine Tartrate