Alpha adrenoceptor regulation of coronary artery blood flow in normal and stenotic canine coronary arteries
Kopia, G.A.; Kopaciewicz, L.J.; Ruffolo, R.R.
Journal of Pharmacology and Experimental Therapeutics 239(3): 641-647
1986
ISSN/ISBN: 0022-3565 PMID: 2879028 Document Number: 268737
The response of systemic blood pressure, heart rate, lead II ECG and left circumflex (LCX) coronary artery blood flow to left cardiac sympathetic nerve stimulation was measured in pentobarbital-anesthetized, open chest, spinal transected and vagotomized dogs. After beta adrenoceptor blockade, left cardiac sympathetic nerve stimulation produced frequency dependent decreases in LCX blood flow. Selective alpha-2 adrenoceptor blockade with idazoxan produced a greater inhibition of this decrease in LCX blood flow than did selective alpha-1 adrenoceptor blockade with prazosin. In an additional population of dogs which were similarly prepared but were not spinally transectioned or pretreated with a beta adrenoceptor antagonist, left cardiac sympathetic nerve stimulation produced an increase in LCX blood flow in all animals which reached a maximum within 40 sec, and then began to decline slowly. However, after beta adrenoceptor blockade, identical stimulation parameters produced only a decline in LCX blood flow which returned to the level of control resting blood flow by the end of the stimulation period. Both selective alpha-2 adrenoceptor blockade with idazoxan and selective alpha-1 adrenoceptor blockade with prazosin produced an inhibition of the LCX blood flow decrease provoked by left cardiac sympathetic nerve stimulation in dogs pretreated with beta adrenoceptor antagonists. Idazoxan produced a slightly greater inhibition of the LCX blood flow decrease than did prazosin, suggesting a greater role for postjunctional vascular alpha-2 adrenoceptors in LCX blood flow regulation during cardiac sympathetic nerve stimulation. The presence of a severe coronary artery stenosis reduced, but did not inhibit, the increase of LCX blood flow in response to cardiac sympathetic nerve stimulation. Beta adrenoceptor blockade in animals with stenotic coronary arteries prevented the stimulation-induced increase in LCX blood flow, but no alpha adrenoceptor-mediated decrease in LCX blood flow was observed as it had been in dogs without stenotic coronary arteries. It is suggested that dilation of the distal coronary bed by means of a stenosis can prevent the alpha adrenoceptor-mediated vasoconstriction which is normally unmasked by beta adrenoceptor blockade. The results indicate that both alpha-1 and alpha-2 adrenoceptors coexist in the canine myocardial circulation, and that both alpha adrenoceptor subtypes mediate coronary artery vasconstriction. In addition, there appears to exist a selective innervation of postsynaptic vascular alpha-2 adrenoceptors in the canine myocardial circulation, with postsynaptic vascular alpha-1 adrenoceptors in resistance vessels being innervated to a lesser degree and possibly having an extrasynaptic distribution. Although both alpha-1 and alpha-2 adrenoceptors may contribute to the regulation of blood flow through normal coronary arteries, alpha adrenoceptors may play a lesser role in blood flow regulation in coronary arteries in which the vasodilatory reserve has been exhausted by the presence of a limiting stenosis.