Effect of Perindopril on Renal Medullary Blood Flow: Comparison With Other Antihypertensive Treatments

Abstract

Early and chronic angiotensin-converting enzyme (ACE) inhibition in Lyfon hypertensive (LH) rats improves their blunted vasodilator response of renal medullary blood flow (MBF) to angiotensin II (AngII). This study examined the specificity of this effect and the possible involvement of nitric oxide (NO). The renal response to AngII (from 7.5 to 480 ng/kg, IV) and acetylcholine (Ach, from 3 to 192 microg/kg, IV) were examined in 12-week-old anesthetized LH rats treated orally from 3 weeks of age with perindopril (1.5 mg/kg/d), nifedipine (50 mg/kg/d), or a triple therapy with hydralazine, hydrochlorothiazide, and reserpine (75, 15, and 0.75 mg/kg/d, respectively). After 9 weeks of therapy, perindopril lowered systolic blood pressure to 113 +/- 3 mm Hg, nifedipine to 144 +/- 4 mm Hg, and triple therapy to 133 +/- 2 mm Hg compared with 160 +/- 3 mm Hg in untreated LH rats. Despite a significant reduction in blood pressure, only the treatment with perindopril significantly increased the vasodilator response of MBF to AngII. However, the vasodilator response of MBF to Ach was similar among the groups. In conclusion, a renal medullary protection is conferred in LH rats by ACE inhibition, an effect that is not obtained with other antihypertensive treatments and is not explained by Ach-induced NO release.

Regulation of Renal Medullary Circulation by the Renin–angiotensin System in Genetically Hypertensive Rats

“…Consequently, the responses to AngII injections were warped. However, we recently observed that the MBF response to acetylcholine is similar between control and perindopril‐treated LH rats 63 . This finding does not support the role of NO in the perindopril‐elicited MBF response and leads us to suggest the major role of PGs, as reported previously in perindopril‐treated LH rats 62 .…”

“…However, it remains unknown whether this effect is related to a reduction in BP. To answer this question, we compared the effects of chronic treatment with either perindopril or nifedipine or triple therapy (hydralazine, hydrochlorothiazide and reserpine; HHR) 63 . After 9 weeks treatment, perindopril, nifedipine and HHR lowered systolic BP to 113 ± 3, 144 ± 3 and 133 ± 2 mmHg, respectively, compared with 160 ± 3 mmHg in untreated LH rats.…”

“…** P < 0.01, *** P < 0.001 compared with untreated LH rats over the doses. Reproduced with permission from Issiakhem et al 63 …”

Angiotensin II and neurohumoral control of the renal medullary circulation

“…To conclude, endogenous AngII does not appear to induce hyperaemia in the medulla under physiological conditions or under any pathological conditions studied to date. There is certainly evidence that hyperaemia induced by exogenous AngII is blunted in some forms of experimental hypertension 39 and can be augmented by antihypertensive treatments, such as angiotensin‐converting enzyme inhibitors, that improve endothelial function, 40 but a direct mechanistic link between these observations and the pathogenesis of hypertension has not been established. However, as we will see below, the mechanisms that mediate AngII‐induced hyeraemia in the medulla likely also contribute to the relative insensitivity of MBF to AngII and other vasoconstrictor factors, such as RSNA.…”