Observations on the mechanism of circulatory autoregulation in the perfused dog's kidney

Abstract

The blood flow through the dog's kidney tends to remain constant despite changes in perfusion pressure. The early observations on this subject have been reviewed by Winton (1937), and recently Selkurt (1951) and Shipley & Study (1951) have shown that the range of perfusion pressure over which the renal flow remains relatively unchanged lies between approximately 90-190 mm Hg. This phenomenon may be present in the isolated kidney and has been referred to as circulatory 'autoregulation'; as it is not known whether its mechanism is active or passive, its relationship to the intrarenal pressure (I.R.P.) and the effect upon it of cyanide have been studied in an attempt to decide this point. METHODSThe experiments were performed on eight dogs anaesthetized with intravenous pentobarbitone and maintained by intravenous supplements as required. After induction and tracheal intubation, the dogs were suspended on a beam by metal hooks through the skin of the back to facilitate retroperitoneal exposure of the kidney through a flank incision. The renal artery was then cannulated, taking care to avoid, as far as possible, the renal nerves, and the kidney was perfused in situ by a mechanical pump with arterial blood supplied from the carotid artery; the renal venous blood returned to the circulation via the intact renal vein. Perfusion pressure could be altered by changes of the stroke output of the pump and the blood flow measured intermittently with a direct flow-meter; changes in flow were also recorded continuously by an electrical flowmeter. Further details of the operation, the direct flow-meter and the pump have been given in previous papers (de Wardener & Miles, 1952; Miles & de Wardener, 1952).In the three dogs in which the effect of cyanide was studied, the renal artery and vein were cannulated in 8ith, and the kidney then removed from the body and placed in 0-9 %(w/v) sodium chloride solution at 380 C. In order to maintain a constant venous pressure the tube from the renal vein was interrupted at a point, arbitrarily fixed 7 cm above the kidney, and the blood allowed to run into a funnel and thence by gravity to the jugular vein. This perfusion circuit, used during the first part of the experiment, is illustrated in Fig. 1. Later, after autoregulation had been demonstrated, and immediately before cyanide was added to the perfusing blood, the tube from the carotid artery was clamped and the renal venous blood was directed to the flow-meter and pump. In this way the circulation of the kidney became completely isolated from the body. Potassium cyanide, freshly dissolved in sodium chloride solution, was then added in an amount calculated to produce an initial concentration of about 4 m.mole/l.

Effect of Hypoxia and Hypercapnic Acidosis on Renal Autoregulation in the Dog: Role of Renal Nerves

“…In these latter studies, RBF autoregulation of the perfused dog kidney remained intact despite perfusate P o 2 as low as 3-7mmHg. It should be noted, however, that interruption of renal oxidative metabolism and induction of histotoxic hypoxia by large doses of intrarenal cyanide may interfere with RBF autoregulation [16]. Together the results of the present studies in vivo and previous perfused kidney studies suggest that RBF and GFR autoregulation occurs despite moderate to profound decreases in arterial or perfusate Po2.…”

Flow as a Function of Arterial Pressure in the Oil Perfused Kidney

“…Thus, as is the case for the kidney perfused with Ringer's solution, r> -° the change in renal resistance when arterial pressure is varied may be concerned largely with the factors determining an abnormally high intraronal pressure. Tn kidneys poisoned with cyanide, the interstitial pressure rises markedly 1 and rectilinear blood pressure-flow data are found.-• 3 A similar relationship between renal arterial pressure and flow has also been observed for an oxygenated colloidal perfusate devoid of red blood cells. * A water-immiscible Newtonian liquid would seem to be an ideal perfusate to determine the purely physical effects of arterial pressure on the dimensional vascular component of renal resistance.…”

“…To assure removal of blood, the heparinized excised kidneys were perfused fii-st with 500 ml. of 1.5 per cent sodium chloride solution 1 " at an arteri'il pressure of 100 mm. Hg.…”

Local Regulation of Blood Flow.

“…A utoregulation o f blood flow through the ren al vascular bed is probably b e t t e r documented (25,29,30,32,34,40,42,48,56,58) than in any other organ in the body. I t has been demonstrated in in ta c t kidneys (29), is o la te d kidneys (25), kidney perfused with oxygenated dextran (25), and in decapsulated kidneys (25).…”

“…However, Haddy e_t a l. (26) found that renal au to reg u latio n was not associated with a s ig n ific a n t change in the rate o f lymph flow from the kidney. Also, autoregulation is said to be abolished upon in a c tiv a tio n of vascular smooth muscle (25,40,42).…”