Autoregulation is the intrinsic ability of an organ to maintain a relatively constant blood flow over a range of perfusion pressures via local active changes in vascular resistance to flow. All previous work on autoregulation of skeletal muscle blood flow has been performed in anesthetized animals. Therefore, the main objectives of this research are to determine conditions that allow the expression of autoregulatory behavior and to evaluate quantitatively the efficiency of autoregulation (i.e., closed-loop gain of flow regulation) during these conditions in the hindlimb vascular bed of conscious dogs. Specifically, we will test the hypothesis that the efficiency of autoregulation of hindlimb blood flow is directly related to the level of tissue metabolism. Dogs will be studied while at rest and during increases in hindlimb oxygen consumption produced by 1) treadmill exercise and 2) pretreatment with 2,4-dinitrophenol. We will also evaluate the role of adenosine as a possible mediator of autoregulation and examine the possible influences of the autonomic nervous system upon hindlimb blood flow autoregulation in conscious dogs. Autoregulatory efficiency will be quantitated from an analysis of hindlimb pressure-flow (P-F) relationships. Three techniques will be used to study the hindlimb P-F relationship: 1) regulation of hindlimb perfusion pressure with an occlusion cuff while measuring flow, 2) controlled flow perfusion via a roller pump while measuring perfusion pressure, and 3) controlled pressure perfusion while measuring flow. The last two techniques are extracorporeal bypass techniques developed by us that allow exploration of hindlimb P-F relationships over wide ranges of pressure and flow in conscious dogs. The importance of understanding blood flow autoregulation stems from the concept that it is one of the mechanisms that operates to match nutrient delivery with tissue metabolic demands. Also, autoregulatory-mediated increases in total peripheral resistance have been suggested to occur in both clinical and experimental forms of hypertension. Our proposed experiments will provide fundamental new information concerning the operation of autoregulation in the hindlimb vascular bed of normal dogs and lead us closer to being able to evaluate autoregulation during the development of renovascular hypertension in conscious dogs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Modified Research Career Development Award (K04)
Project #
1K04HL001515-01
Application #
3073840
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1985-08-01
Project End
1990-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Toledo
Department
Type
Schools of Medicine
DUNS #
807418939
City
Toledo
State
OH
Country
United States
Zip Code
43614
Skarlatos, S; DiPaola, N; Frankel, R A et al. (1993) Spontaneous pressure-flow relationships in renal circulation of conscious dogs. Am J Physiol 264:H1517-27
Frankel, R A; Metting, P J; Britton, S L (1993) Evaluation of spontaneous baroreflex sensitivity in conscious dogs. J Physiol 462:31-45
Koch, L G; Strick, D M; Britton, S L et al. (1991) Reflex versus autoregulatory control of hindlimb blood flow during treadmill exercise in dogs. Am J Physiol 260:H436-44
Stoos, B A; Metting, P J; Britton, S L (1991) Autoregulatory capacity in renal and mesenteric vasculatures of mineralocorticoid hypertensive dogs. Am J Physiol 261:H1205-13
Brand, P H; Coyne, K B; Kostrzewski, K A et al. (1991) Pressure diuresis and autonomic function in conscious dogs. Am J Physiol 261:R802-10
Koch, L G; Britton, S L; Metting, P J (1990) Adenosine is not essential for exercise hyperaemia in the hindlimb in conscious dogs. J Physiol 429:63-75
Metting, P J; Stein, P M; Stoos, B A et al. (1989) Systemic vascular autoregulation amplifies pressor responses to vasoconstrictor agents. Am J Physiol 256:R98-105
Metting, P J; Kostrzewski, K A; Stein, P M et al. (1989) Quantitative contribution of systemic vascular autoregulation in acute hypertension in conscious dogs. J Clin Invest 84:1900-5
Metting, P J; Strader, J R; Britton, S L (1988) Evaluation of whole body autoregulation in conscious dogs. Am J Physiol 255:H44-52
Brand, P H; Metting, P J; Britton, S L (1988) Support of arterial blood pressure by major pressor systems in conscious dogs. Am J Physiol 255:H483-91

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