Is the humoral renal antihypertensive activity of the spontaneously hypertensive rat (SHR) reset to the high blood pressure?

Abstract

The kidneys have a humoral antihypertensive system, located in the renal medulla and presumably antagonizing the pro-hypertensive renin-angiotensin system. Medullipin I and II and maybe platelet activating factor (PAF), seem to be the mediators of this system, known to be activated after reversal of renovascular hypertension or when the perfusion pressure to a normotensive kidney is suddenly elevated. The present study was undertaken to investigate whether this system is functioning also in the spontaneously hypertensive rat (SHR), and if it is then reset in proportion to the increased mean arterial pressure (MAP). Isolated kidneys from spontaneously hypertensive rats and from Wistar Kyoto rats (WKY) were cross-perfused in vivo from anaesthetized intact Wistar Kyoto rat 'donors'. After 30 min of perfusion at 100 mmHg the perfusion pressure to the isolated kidneys were, for 60 min, either kept unaltered at 100 mmHg or, for the Wistar Kyoto rat kidneys, increased to 150-200 mmHg and, for the spontaneously hypertensive rat kidneys, raised to 200 or 250 mmHg. The results show that the humoral antihypertensive system is present also in spontaneously hypertensive rat kidneys, but is here reset upwards to or even beyond the elevated MAP level. Furthermore, all mean arterial pressure reductions caused by high-pressure perfusion of Wistar Kyoto and spontaneously hypertensive rat kidneys were accompanied by reductions in heart rate (HR) in the 'donors', in agreement with previous observations after reversing renal hypertension and after i.v. medullipin I injection. In fact, in spontaneously hypertensive rat kidneys, the 'incretory' depressor mechanism appears to be more markedly reset upwards than is the 'excretory' depressor mechanism inherent in pressure diuresis with consequent salt-volume elimination. In conclusion spontaneously hypertensive rats, like Wistar Kyoto rats and Wistar rats, have a humoral antihypertensive system in the kidneys, but it is reset upwards even beyond the elevated mean arterial pressure level in spontaneously hypertensive rats. The combination of a depressor response and reduced heart rate in the 'donors' renders further evidence that the medullipins are the principal, though probably not the only, humoral antihypertensive factors released from the cross-circulated kidneys.