Neurogenic components of hypertension in human renal artery stenosis

In renal artery stenosis activation of the renin-angiotensin system elevates blood pressure by direct peripheral effects and probably through stimulation of sympathetic activity, which can be induced by angiotensin-II either centrally or peripherally. In animals specific brain lesions and afferent renal denervation can either attenuate or prevent renovascular hypertension. We investigated the neurogenic mechanisms responsible for hypertension in 21 patients with unilateral renal artery stenosis off drug therapy, by studying the cardiovascular and hormonal effects of Clonidine. The responses to Captopril served as an indicator of the peripheral effects of angiotensin-II. Both oral and intravenous Clonidine lowered blood pressure substantially and for a prolonged period even in patients who had been refractory to multiple antihypertensive drug therapy. Levels of plasma renin activity were unchanged after Clonidine. Plasma noradrenaline levels fell. Pressor responses to infused angiotensin-II were not reduced. These data suggest that Clonidine lowers blood pressure independently of hormonal and peripheral vascular interactions and is consistent with its predominantly central sympatholytic effects. Oral Captopril, unlike Clonidine, had variable hypotensive effects directly related to the basal level of plasma renin activity. The largest reductions were observed in those with the highest level of renin. Our studies indicate that neurogenic mechanisms, probably centrally mediated, have an important and often major role in maintaining hypertension in human renal artery stenosis. These may result from the central effects of angiotensin-II, and/or from increased afferent renal nerve activity, as demonstrated experimentally. The neurogenic components maintaining hypertension in renal artery stenosis are largely dependent on renal ischaemia as revascularisation (by surgery or angioplasty) or nephrectomy, either ameliorates or cures the hypertension in the majority of our patients.