Key result
RAS blockade with Sq20881 drops BP for ~6 hours in nephrectomized rats, supporting arterial renin's role.
Why the study?
The role of renin within arterial and arteriolar walls in maintaining blood pressure in hypertension remains unclear despite plasma renin measurements.
Preclinical evidence suggests that renin within the arterial and arteriolar wall, rather than circulating plasma renin, is responsible for blood pressure maintenance.
Hypothesis-generating for tissue renin in BP maintenance; leaves open human relevance and therapeutic translation.
Whilst plasma renin values are elevated in a minority of patients with essential hypertension, there is no indication that high renin hypertension is a distinct entity and even where renin levels are elevated, they are usually less than those observed in renovascular hypertension. It is still possible for the renin-angiotensin system to be important, if blood pressure is maintained by renin activity within the arterial or arteriolar walls. Accordingly, renin-like activity or rat aortic wall homogenate and plasma renin concentrations were measured simultaneously. Both plasma and aortic renin (measured with an incubation pH of 6.5) rose in salt-depleted and fell in salt-loaded rats. Both were elevated in Goldblatt 2-kidney hypertension. However, aortic renin fell gradually over 24 h after bilateral nephrectomy, whilst plasma renin had reached its nadir by 1 h. To assess the importance of arterial as opposed to plasma renin the renin-angiotensin system was blocked with the converting enzyme inhibitor Sq20881. A blood pressure fall attributable to renin-angiotensin blockade could be demonstrated for at least 6 h after bilateral nephrectomy. This supports the hypothesis that renin in the arterial and arteriolar wall, rather than plasma renin, is responsible for blood pressure maintenance. Nevertheless, in steady state conditions such as essential hypertension, plasma and arterial renin are closely related.
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J. D. Swales (2008) studied Hypertension. Converting enzyme inhibitor Sq20881 was evaluated on Blood pressure fall. Blockade of the renin-angiotensin system with Sq20881 caused a blood pressure fall for at least 6 hours after bilateral nephrectomy in rats, supporting arterial renin's role in BP maintenance.
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