Function of the isolated spontaneously hypertensive rat kidney after blood pressure reduction.

We treated 20-week-old spontaneously hypertensive rats (SHR) with either placebo or hydralazine, reserpine and hydrochlorothiazide for 1 month. Mean arterial pressure in treated SHR averaged 113 +/- 7 mm Hg (mean +/- SE), compared to 162 +/- 12 mm Hg in animals receiving placebo (p less than 0.01). Glomerular filtration rate (GFR) and sodium excretion were similar in both groups. In isolated perfused kidneys, the GFR and sodium excretion were significantly greater in the treatment group than in the placebo group at a perfusion pressure of 140 mm Hg (p less than 0.01). Renal vascular resistance (RVR) of kidney from treated SHR was no different from RVR of kidney from placebo SHR. Hydralazine (6 mM) and diazoxide (4 mM) increased the GFR and sodium excretion of isolated SHR kidney perfused at 140 mm Hg (p less than 0.05), but decreased RVR significantly (p less than 0.05). We conclude that prolonged antihypertensive treatment renders higher GFR values to isolated SHR kidneys perfused at 140 mm Hg, with sodium excretion varying in proportion to the GFR. The addition of vasodilators to the perfusate of isolated SHR kidneys partially reproduced these changes, but only at extremely high concentrations unlike to be attained in vivo.

Function of the arachidonate-deficient spontaneously hypertensive rat kidney.

In order to assess the effect of renal prostaglandins on the glomerular filtration rate (GFR) and electrolyte excretion in the spontaneously hypertensive rat (SHR), we perfused isolated SHR and normotensive Wistar-Kyoto (WKY) kidneys after pretreatment with either a control diet or a diet deficient in arachidonate, the precursor of prostaglandins. When perfusion pressures were increased from 100 to 160 mm Hg, renal vascular resistances (RVR) increased by 32-41%. RVR of SHR kidneys always exceeded that of WKY kidneys by a nearly constant amount, and arachidonate deficiency had little effect on this relationship. In contrast to RVR, the GFR increased severalfold. GFR and urine flow were greater in WKY than in SHR kidneys, a relationship unaffected by arachidonate deficiency. Changes in sodium and chloride excretion occurred in parallel with GFR. Although arachidonate-deficient SHR and WKY kidneys manifested potassium wastage compared to controls, arachidonate deficiency did not result in altered sodium or chloride excretion. The results suggest that direct actions of arachidonate or renal prostaglandins are not responsible for most functional differences between SHR and WKY kidneys.

Pressure-dependent action of angiotensin II on glomerular filtration in the isolated rat kidney.

We examined the action of angiotensin II (AII) on isolated rat kidney perfused with a recirculating cell-free solution at either 12 pKa (90 mmHg) or 17 kPa (128 mmHg). The renal perfusion pressure was maintained constant while sufficient AII was added to increase the renal vascular resistance by 50%. In the low-pressure kidneys. AII increased the glomerular filtration rate (GFR) by 155%, increased sodium reabsorption by 157%, and decreased the urine sodium concentration by 34% without affecting sodium excretion. In the high-pressure kidneys, GFR initially was significantly greater but was not affected by AII. In these experiments, AII had no effect on sodium reabsorption or excretion and decreased the urine sodium concentration by 7%. The data suggest that AII could be involved in autoregulation of the GFR without producing large changes in sodium excretion.

Actions of angiotensin II on the isolated spontaneously hypertensive rat kidney.

We studied the effects of angiotensin II (AII) on isolated spontaneously hypertensive rat (SHR) and Wistar-Kyoto control (WKY) kidneys utilizing a recirculating cell-free perfusate. Sufficient AII was infused to increase renal vascular resistance (RVR) by approximately 50%. When the perfusion pressure was allowed to increase with RVR during AII infusion, significant increases in the glomerular filtration rate (GFR), urine flow, and electrolyte excretion occurred in both the SHR and the WKY kidneys. However, when the increase in perfusion pressure was prevented, AII increased the GFR of SHR kidneys but had no effect on the GFR of WKY. In contrast to WKY, AII increased the GFR, urine flow, and sodium excretion of SHR kidneys as much at "normotensive" perfusion pressures as at "hypertensive" pressures. However, the "normotensive" perfusion pressures utilized in these studies were less than the blood pressure of the SHR in vivo. Accordingly, the response of SHR kidneys to AII was assessed when perfusion pressure was maintained constant at 160 torr. Under these conditions, AII did not elicit any further increases in GFR or changes in the electrolyte excretion. Results indicate that the renal perfusion pressure is a critical determinant of the renal responsiveness to AII and suggests that AII enhances renal function at perfusion pressures less than those customarily encountered in vivo.

Acid-base maneuvers and phosphate transport in the isolated rat kidney.

The influence of bicarbonate (HCO3-), the carbon dioxide tension (PCO2), and pH on phosphate (Pi) excretion were assessed in isolated rat kidneys, perfused in vitro with recirculating synthetic solutions. After establishing control values, the perfusate HCO3- or PCO2 was altered separately. When the perfusate pH was decreased, either by increasing PCO2 or decreasing HCO3-, the absolute and fractional Pi excretions increased. Perfusate alkalinization by slightly decreasing the PCO2 did not affect Pi excretion, but increasing the perfusate pH with addition of HCO3- elicited phosphaturia. Other kidneys were perfused with a solution from which the CO2/HCO3- buffer system was nominally absent. Alkalinization of HCO3--free perfusate had no effect upon Pi excretion, but acidification resulted in marked phosphaturia. Perfusate acidification, whether achieved by decreasing HCO3-, increasing PCO2, or by adding hydrogen ions, uniformly elicited phosphaturia. The data indicate that either decreasing the extracellular pH or increasing the extracellular HCO3- inhibits renal Pi reabsorption.