Effect of nitroglycerin on total and regional coronary blood flow in the normal and ischaemic canine myocardium

Adenosine is thought to participate in local regulation of coronary blood flow. However, competitive antagonists of adenosine fail to block myocardial active hyperemia. We examined the effect of locally administered theophylline on active hyperemia and myocardial adenosine production during intracoronary isoproterenol infusion in the dog heart. Isoproterenol decreased coronary resistance and increased myocardial adenosine production. Infusion of theophylline at a rate that attenuated the vasodilator response to exogenously administered adenosine failed to attenuate the increase in coronary blood flow produced by isoproterenol. However, theophylline plus isoproterenol produced greater increases in myocardial adenosine production than isoproterenol alone. The curves relating resistance and adenosine in the presence of theophylline fell to the right of those in the absence of theophylline. These findings suggest that the failure of theophylline to attenuate isoproterenol hyperemia in the dog heart results at least in part from an increase in adenosine concentration at the arteriole to a level beyond that blocked by this competitive antagonist and that adenosine may in fact play a role in isoproterenol-induced active hyperemia.

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Desensitization of myocardial but not coronary VIP receptor-mediated responses in dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1988.255.3.h601 ◽

1988 ◽

Vol 255 (3) ◽

pp. H601-H607 ◽

Cited By ~ 2

Author(s):

F. L. Anderson ◽

A. C. Kralios ◽

R. Hershberger ◽

M. R. Bristow

Keyword(s):

Blood Flow ◽

Coronary Blood Flow ◽

Left Ventricular ◽

Before And After ◽

Pressure Development ◽

Heterologous Desensitization ◽

Group A ◽

Homologous Desensitization ◽

Isoproterenol Infusion ◽

Canine Myocardium

Desensitization to the hemodynamic effects of vasoactive intestinal polypeptide (VIP) was examined in 12 anesthetized, open-chest dogs in which cardiac output, systemic arterial resistance, and heart rate were fixed. VIP was administered by intracoronary infusion, and the effects were compared with isoproterenol and forskolin. Measurements of left ventricular maximum rate of pressure development (dP/dt), coronary blood flow, and myocardial oxygen consumption were made before and after a 90-min infusion of either isoproterenol (6 dogs) or VIP (6 dogs). After isoproterenol infusion, there was a significant decrease in the effect of isoproterenol on left ventricular dP/dt and coronary blood flow. The effects of VIP and forskolin were not changed. After VIP infusion, there was a significant decrease in the effect of VIP on left ventricular dP/dt with no change in the effects of isoproterenol and forskolin. In this group, a significant increase in coronary blood flow with minimal change in myocardial oxygen could still be elicited by VIP injection after VIP infusion. The agonist infusion time to achieve a decrease in inotropic effect was less for VIP when compared with isoproterenol. Thus these data demonstrate acute homologous desensitization of myocardial VIP and beta-adrenergic receptors in canine myocardium with no development of heterologous desensitization, desensitization involving the catalytic subunit of adenylate cyclase, or desensitization of the VIP-mediated primary coronary vasodilator response.

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