Coronary collateral development and function in conscious dogs

J Mol CellCardiol23 (Supplement III) (1991) B-2-2

CORONARY

COLLATERAL

DEVELOPMENT

AND

FUNCTION

IN

CONSCIOUS

DOGS

Hiroyuki Hanada, Daniel McRown, Michael M&own. Dean Franklin, Dalton Research Center and Department of Physiology, University of Missouri, Columbia, MO 65211. We previously demonstrated that repetitive episodes of regional, reversible myocardial ischemia constituted an adequate stimulous for coronary collateral development in conscious dogs, instrumented for measurements

of

regional

myocardial

function

and

blood

We now

flow.

present the use of this animal model for studies of interventions purported to modify the rate of development of collaterals and the effects

of

various

mature collaterals. potential sources

B-2-3

ENDOTHELIAL

interventions

on collateral

Examples of the results of error are identified.

PURINE

METABOLISM:

A ROLE

IN

perfusion

in

dogs

are illustrated

REGULATING

with

and

VASOMOTION?

James B. Bassingthwaighte, Keith Kroll, Lisa M. Schwartz, Thomas R. Bukowski, James H. Revkin. University of Washington WD-12, Seattle WA 98195. Although it is logicsl to suppose that the myocyte has the prime role in regulating the state of vasomc+ tion at moments of metabolic stress on the heart, this is not proven. It is equally reasonably conceivable that the endothelium has a prominent influence, and in fact could even be the mediator for responses to signals from cardiomyocytes. Adenosine (Ado) and inosine metabolism in endothelial cells domlna,te the exchanges between blood and myocytes; hypoxanthine (Hx) and xanthine metabolism take place solely in endothelial cells, so purine salvage via Hx reincorporation into IMP must be influenced at least in part by the endothdial reactions. Indicator dilution studies using the various purine tracers plus reference indicators gives good measures of endothelial permeability surface area products at varied concentration of substrate, and so give K, and V,,, for transporters. Intrsendothelial reactions occur with lower K,‘s than those for transport. Because the transporter and transformation enzymes are different from organ to organ and from species to species, we have worked out the regulatory scheme for only 1 species, the guinea pig, and for myocardial capillaries only. However the style of approach is general. The information gained on this species argues that when Ado is being released from the heart, its concentration is higher in the ISF than in the effluent plasma. Therefore the endothelium limits purine loss from the heart, apparently serving

as a transient

reservoir,

and probably

returning

it to the myocyte

as Hx.

Endothelial

cekls and

cardiomyocytes thus interact to regulate ISF levels of Ado. (Supported by HL19139 and HL38736.1)

B-2-4

PHYSIOLOGIC ROLE OF SNDOGENOUS NITRIC OXIDE ON BASAL TONE AND NNDOTNELIUN-DEPENDENT RESPONSES OF EPICARDIAL AND RNSISTANCE CORONARY ARTERIES IN AWAKE DOGS Frederick R. Cobb, David E. Chambers, William D. Knehl, Richard M.J. Palmer, Salvador Moncada, Alan Chu, Duke & VA MC, Durham, NC, USA & Wellcome Res Lab, Beckenham, England Basal epicardial coronary diameter, acetylcholine-stimulated endothelium-dependent dilation and flow-induced endothelium-dependent dilation of the epicardial arteries (dimension crystals) and phasic blood flow (Doppler probes) were recorded before, and after 5, 15, 50 and 120 mg/kg of NO-monomethyl-L-arginine (L-NNMA), a specific inhibitor of nitric oxide formation. L-NMMA induced a dose related epicardial coronary vasoconthe maximum decrease was 8% representing an - 15% decrease striction, in crosssectional area. There was an accompanying increase in aortic pressure and a decrease in heart rate. At doses 2 50 mgfkg, rest coronary blood flow was also decreased. In contrast, the flow-induced or acetylcholine-stimulated endothelium-dependent responses were attenuated approximately 50% only after infusion of the highest doses of L-NMNA The changes in the basal vasomotor tone and acetylcholine-stimulated en(120 mg/W). dothelium-dependent responses returned towards the control states in the presence of Larginine (660 mg/kg). These data support the view that nitric oxide plays a significant role in modulating basal vaeomotion and endothelial dependent dilation stimulated by acetylcholine or increases in blood flow in epicardial coronary arteries and also influences the regulation of coronary blood flow during physiologic conditions. 5.13