The aim of this proposal is to study the characteristics of resistance arteries in the kidney and their regulation by certain neural (noradrenergic and possibly dopaminergic and cholinergic) and humoral (angiotensin and prostaglandin) control mechanisms. Relatively little is known from direct in vitro experimentation of this important class of vessels (resistance arteries) and virtually nothing concerning those arteries located in the kidney. Functional features of the innervation, smooth muscle and endothelium of rabbit renal arteries as small as 50 MuI.D. will be documented by the utilization of a resistance vessel myograph and structural and biochemical measurements. These features will be related to vessel diameter and/or location in the kidney. The specific objectives of research include: (1) determination of how nmoradrenergic control varies with artery diameter and/or kidney location, (2) pharmacological classification and functional description of rabbit renal vascular dopamine receptors, (3) determination of the presence of a rabbit renal dopaminergic innervation and investigation of the possibility of a neurogenic vasodilator mechanism involving dopamine, (4) determination of the presence of an endothelial-dependent acetylcholine mediated vasodilation response inversely proportional to vessel diameter and investigation of the possibility of a neurogenic vasodilator mechanism in renal arteries involving acetylcholine and (5) pharmacological and functional description of the direct response to angiotensin in renal arteries. Specific objectives 1 and 5 require some delineation of the modulation of vasoconstrictor influences in the renal arteries by endogeneous prostaglandins and determination of the dependency of that modulation on an intact endothelium. The overall objective is to understand changes that occur in vessel characteristics with change in their diameter and/or location in the kidney. Although resistance arteries in general play a pivotal role in circulatory function and appear to be altered in hypertension, only recently have direct studies of any of these vessels been undertaken in vitro. In spite of the fact that renal blood flow constitute 15-25% of cardiac output and is therefore of general circulatory interest, this represents the first detailed in vitro study to be undertaken in renal resistance arteries.
| Owen, M P; Taphorn, M C; Walmsley, J G (1989) Adrenergic control of intrarenal arteries of rabbits. Am J Physiol 256:H607-12 |
| Owen, M P; Joyce, E H; Bevan, J A (1987) Sources of activator calcium for extrinsic vascular tone and nimodipine inhibition of that tone in proximal vs. distal rabbit ear arteries. J Pharmacol Exp Ther 243:27-34 |
