Effects of antihypertensive treatment in one-clip, two kidney hypertension in rats

In order to investigate the consequences of antihypertensive therapy on hormonal and renal parameters in one-clip, two kidney renovascular hypertension, we compared the effects of converting enzyme inhibition (CEI) with those of tripletherapy (clonidine, dihydralazine and furosemide) in this experimental model in rats. The treatment period was initiated four weeks after application of the clip and was continued for five weeks. In plasma, renin was increased and renin substrate was negatively correlated to plasma renin. Hypertension was associated with activation of the renin angiotensin system in both plasma and kidney. The degree of activation of the renin-angiotensin system in the clipped kidney and its suppression in the unclipped kidney was evaluated by two methods, renal renin content and semi-quantification of juxtaglomerular hyperplasia by immunofluorescent renin. These two methods were correlated. During the treatment period, average systolic blood pressure was 144 +/- 13 mmHg in the CEI treated group (HT1) which was not significantly different from the value found in the sham-operated group (139 +/- 4 mmHg; C2). Blood pressure, however, was lowered only to 173 +/- 18 mmHg in the group treated with tripletherapy (HT2). In control hypertensive animals, the wt of the clipped kidney did not decrease whereas significant hypertrophy was present in the unclipped kidney. Tripletherapy did not alter this relationship, whereas converting enzyme inhibition decreased kidney wt in the clipped kidney and increased further the hypertrophy of the contralateral unclipped kidney. A histological examination revealed that hypertensive microangiopathy was a predominant feature in the unclipped kidney of the untreated hypertensive group and of the group treated with tripletherapy, these lesions were completely absent in the CEI treated group. In the CEI treated group, however, ischemic lesions during this treatment were found to be decreased in the contralateral unclipped kidney and increased in the clipped kidney by comparison with untreated hypertensive rats. These renal lesions observed in the clipped kidney were most likely related to the normalization of blood pressure or to a disturbance of intrarenal mechanisms normally mediated by the renin-angiotensin system during stenosis of a renal artery.