J. Rudenstam

Influence of the renal medulla and early treatment with enalapril upon the development of hypertension in young spontaneously hypertensive rats.

Objective: To investigate the role of the renal medulla in early hypertension in spontaneously hypertensive rats (SHR), and to explore whether the attenuated increase of pressure induced by enalapril treatment is affected by chemical medullectomy Design: Forty-four male SHR were studied from 5 to 18 weeks of age: 22 remained intact; 22 were medullectomized at 5.5 weeks of age with 2-bromoethylamine hydrobromide; 11 of each of these two groups were treated with enalapril from 6 to 12 weeks of age. Blood pressure, heart rate and body weight were recorded intermittently, and at 18 weeks renal function was also analysed Results: The results indicate a protective effect of the renal medulla against severe pressure rises in SHR, although even when enalapril also lowered blood pressure in medullectomized SHR, persistent improvements of glomerular filtration rate and renal flow conductance occurred only in intact SHR. Furthermore, after enalapril treatment ended blood pressure rose to higher levels in medullectomized SHR, despite greater sodium—water losses Conclusion: The renal medulla seems to exert a protective role both during and after enalapril treatment.

Do angiotensin converting enzyme inhibitors lower blood pressure in the rat partly via the humorally mediated antihypertensive system of the renal medulla

It has been suggested that there is a negative-feedback interaction between the humoral renomedullary antihypertensive system and angiotensin II. If so, the acute blood pressure-lowering effects of angiotensin converting enzyme (ACE) inhibitors might be due, in part, to an increased secretion of renomedullary depressor substances. Groups of anaesthetized Wistar-Kyoto rats (WKY) with an intact or chemically destroyed renal medulla received either saline or the ACE inhibitor enalapril, and mean arterial pressure (MAP), heart rate and renal function were measured. MAP was clearly decreased after enalapril administration in the WKY controls with an intact renal medulla, but was not changed in the medullectomized group. In one WKY control group, where the prostaglandin and kallikrein-kinin systems had also been acutely blocked, the MAP reduction after enalapril was even more marked than in the intact controls. Thus, the acute blood pressure-lowering effect of enalapril is clearly dependent on an intact renal medulla, further suggesting that the renomedullary antihypertensive system is important to normal blood pressure homeostasis.

Effects on regional renal blood flow when unclipping a two-kidney, one-clip hypertensive Wistar rat during renal nerve stimulation.

Blood pressure (BP) is rapidly normalized when removing the obstruction from the renal artery of a two-kidney, one-clip renovascular hypertensive rat (unclipping). This study tested whether efferent renal nerve stimulation (ERNS) of the unclipped kidney affects this drop in BP or the associated changes in diuresis-natriuresis and regional renal blood flow. Three groups of anesthetized renovascular hypertensive Wistar rats were studied: 1) W(C) (time control); 2) W(UC) (unclipped after 30 min); and 3) W(UC+NS) (unclipped after 30 min, with ERNS at 5 Hz for 2 h). Renal excretion and regional hemodynamics (laser Doppler) were monitored in the unclipped kidney. Medullary and cortical blood perfusion increased by 84% and 95%, respectively, in W(UC) 30 min after unclipping (P < .001) but only with 8% and 9%, respectively, in W(UC+NS) (P = NS). Unclipping induced a marked increase in diuresis-natriuresis that was largely unaffected by ERNS. In W(UC) and W(UC+NS) BP returned to normotensive levels within 4 h. However, during the first 30 min, average BP decreased significantly less in W(UC+NS) (9%, 20 mm Hg) than in W(UC) (16%, 35 mm Hg) (P < .05). ERNS at 5 Hz effectively prevented the increase in medullary blood perfusion but did not affect the fall in blood pressure or the pressure diuretic/natriuretic response seen after unclipping. The results suggest that both the reduction in BP and the pressure-induced increase in diuresis/natriuresis seen when unclipping the 2K,1C renovascular hypertensive rat occurs largely independently of ERNS and an increase in medullary blood perfusion.