Key result
Combined blockade with captopril and phenoxybenzamine normalized mean arterial pressure to 86.7 mmHg (p<0.001) in rats with chronic two-kidney, one-clip hypertension.
Why the study?
Does inhibition of the renin-angiotensin and sympathetic nervous systems reduce mean arterial pressure in rats with chronic two-kidney, one-clip hypertension?
Does inhibition of the renin-angiotensin and sympathetic nervous systems reduce mean arterial pressure in rats with chronic two-kidney, one-clip hypertension?
p-value: p=<0.001
Both the renin-angiotensin system and the sympathetic nervous system are required to maintain high blood pressure in the chronic phase of two-kidney, one-clip hypertension in rats.
Both systems sustain chronic renovascular hypertension in rats; hypothesis-generating for dual blockade but leaves open human translation.
The purpose of the present study was to examine the role of the renin-angiotensin and the sympathetic nervous systems during the chronic phase (greater than 16 weeks) of two-kidney, one-clip hypertension in conscious unrestrained rats. During this phase, the mean arterial pressure (MAP) (p less than 0.001) and plasma angiotensin II (31.9 +/- 1.5 to 125.8 +/- 19.9 pg/ml, p less than 0.005) were significantly increased as compared to normotensive group. Converting enzyme inhibition by captopril produced a significant decrease of MAP (181.2 +/- 8.2 to 140.0 +/- 5.5 mmHg, p less than 0.001). This hypotensive response was similar when aprotinin (a Kallikrein inhibitor) and captopril were infused simultaneously. Alpha 1-adrenergic receptor blockade by phenoxybenzamine (POB) significantly decreased but did not normalize MAP (179.8 +/- 12.4 to 135.8 +/- 10.4 mmHg, p less than 0.001). However, when infused after POB, captopril induced a further decrease of MAP to 86.7 +/- 9.4 mmHg (p less than 0.001). This MAP level was not different from that found in normotensive rats after infusion of the two drugs (83.2 +/- 5.3 mmHg). These results suggest that both the renin-angiotensin system and the sympathetic nervous system, by activating peripheral alpha 1-adrenergic receptors, maintain the high blood pressure during the chronic phase (greater than 16 weeks) of two-kidney, one-clip hypertension in conscious rats.
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Salazar et al. (1985) studied Two-kidney, one-clip hypertension. Captopril and phenoxybenzamine vs. Normotensive group / baseline was evaluated on Mean arterial pressure (MAP) (p=<0.001). Combined blockade with captopril and phenoxybenzamine normalized mean arterial pressure to 86.7 mmHg (p<0.001) in rats with chronic two-kidney, one-clip hypertension.
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