Cause of Genuine Autoregulation of the Renal Circulation

Abstract

The mechanism causing renal vascular flow to vary less than proportional to changes in arterial-venous pressure gradient, was studied in isolated dog kidneys perfused with whole blood and with cell-free colloidal solutions. This autoregulation of renal flow rapidly deteriorated along with vascular reactivity to drugs when oxygenated polyvinyl-pyrrolidone-Locke solution was used for perfusion. This deterioration was prevented by the addition of plasma to the colloidal perfusate. During the first 2 seconds of suddenly raised arterial pressure, renal flow normally increased proportionately or slightly more than proportionately to the increase in arterial pressure; intrarenal venous pressure, needle tissue pressure and kidney weight rose simultaneously. During the next 4 seconds, increasing vascular resistance upstream from the intrarenal veins caused parallel reductions in renal flow, intrarenal venous pressure, needle tissue pressure and at times kidney weight. After brief rhythmical changes in prevenous segmental resistance, flow became steady to show intense autoregulation, while intrarenal venous pressure and needle tissue pressure remained relatively low. This genuine autoregulation of renal flow was abolished by cooling kidneys to 3 to 10 C, and by treatment with chloral hydrate and with procaine in concentrations rendering the smooth muscle of the renal blood vessels relatively inert to direct drug stimulants. On the other hand, at temperatures of 3 to 10 C., and usually with chloral hydrate treatment, a factitious and passive type of flow autoregulation was observed, caused by the effects of abnormally high tissue pressures. Renal flow autoregulation was not appreciably impaired by anesthetization of the intrarenal nerves by procaine in concentrations which did not simultaneously depress vascular smooth muscle reactivity. Yohimbine induced sympatholysis did not impair autoregulation, and Dibenzyline treatment to intrarenal sympatholysis depressed only slightly autoregulation of renal flow. It was not inhibited by γ-aminobutyric acid. Anoxic perfusion which did not appreciably depress the reactivity of intrarenal autonomic ganglia, impaired autoregulation moderately. The loss of autoregulation of renal flow, accompanied by vasoconstriction following severe hemorrhage in the kidney donor dog, was slowly reversible upon perfusion of the subsequently isolated kidney and was related to smooth muscle contracture within the arterial-arteriolar vasculature. It is concluded, that myogenic vasomotion in the renal arterial-arteriolar tree in response to the level of transmural vascular pressure is the fundamental cause of genuine renal circulatory autoregulation. It is furthermore suggested that the myocytes of the juxtaglomerular apparatus may act as myogenic pacemakers in the vasomotion responsible for the essentially perfect autoregulation of the normal kidney.

Intrinsic Regulation of Skeletal Muscle Blood Flow

“…The phenomenon of autoregulation has been reported for several vascular beds including kidney, 2 intestine, 3 ' 4 brain, 5 and heart. 0 A number of investigators '• 7 " n have confirmed the early observations of Bayliss 12 who reported autoregulation in skeletal muscle.…”

Esmolol attenuates hepatic blood flow responses during sodium nitroprusside-induced hypotension in dogs

“…It is more likely that the reductions in RBF in all three groups were due to hypotension beyond the normal range of renal autoregulation, because RBF intrinsically autoregulates with change in MAP from 80 to 180 mmHg in dogs. 22 In addition, SNP has only a weak vasodilating activity on the renal vasculature. 23,24 Because hypotension within the autoregulatory pressure range of the renal vasculature has been shown to result in redistribution of blood flow from the outer cortical layers to juxtamedullary layers, 25 mechanisms responsible for RBF reductions may cause a maldistribution of RBF within the autoregulation process.…”

Absence of Renal Circulatory Autoregulation during Perfusion with Paraffin Oil

“…Autoregulation was tested during both aqueous and oil perfusions by rapidly induced changes in renal arterial pressure, with observance of whether square wave changes in pressure were associated with square wave changes in organ outflow [30] or with rapid phasic adjustments in flow rate [30]. Steady state flow rates were meas ured directly shortly before arterial pressure elevation, after 1.5-2 min of raised arterial pressure, and again 1-2 min after reduction of arterial pressure to a level near the initial 'control' perfusion pressure.…”

“…In 4 of 9 dog kidneys, reuse of once-perfused colloidal solution was required before autoregulation was well manifested, because of the finding of little or not autoregulation during the first 10-20 min of isolated perfusion with synthetic colloidal solution, as previously found when the colloidal perfusate was devoid of plasma [30], and because of depletion of the initial reser voir supply of colloidal perfusate.…”

“…The resistance changes that bring about autoregulation of RBF and GFR have been attributed usually to myogenic changes in arteriolar resistance in response to the magnitude of transmural pressure or of vessel wall tension [ 12,19,23,26,27,30]. How ever, several chemical hypotheses for the mechanism underlying renal circulatory autoregulation are also current [10,16,19,24,27],…”