The effect of chemical damage to the renal medulla on its antihypertensive function.

Abstract

Renomedullary antihypertensive function was studied in rats in which the renal medulla was chemically damaged either by chronic ingestion of high doses of aspirin (the rats were treated for 6 months before the experiment with aspirin at 300 mg/kg/day) or by a single injection of bromethylamine hydrobromide (BEA) (50 mg/rat, i.v., two months before the experiment). The results were compared to those from control, nontreated rats. When placed on a high salt intake (1% NaCl solution was offered instead of drinking water), the rats with aspirin-induced renomedullary damage and the controls did not develop hypertension during the 12-week period of salt loading, while the animals treated with BEA developed high blood pressure (systolic pressure over 20 kPa) by the sixth week. In the second experiment, renal medullae taken from control, aspirin-treated, and BEA-treated rats were transplanted to rats with chronic one-kidney one-clip hypertension, and the potency of medulla taken from the three different groups in lowering blood pressure in the hypertensive recipients was compared. A significant decrease in blood pressure of about 4–5 kPa was observed in the hypertensive rats which received transplants of medullae taken from control and aspirin-treated rats; whereas no significant change in blood pressure was observed in the hypertensive rats which received transplants of medullae taken from BEA-treated rats, or which were sham-transplanted. The results indicate that the deficiency of renomedullary antihypertensive function is an event conducive to the development of salt hypertension in rats, i.e., an increase in blood pressure in response to salt loading was observed only in animals in which the antihypertensive function of the medulla was decreased, as determined by the inability of renomedullary transplants to lower blood pressure in hypertensive recipients. Furthermore, the present data indicate that aspirin-induced renomedullary damage does not abolish renomedullary antihypertensive function; and thus the notion that hypertension associated with aspirin abuse nephropathy results from aspirin-induced renomedullary deficiency appears to be unlikely.