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

• Published in: Kidney international Vol. 29; no. 5; pp. 1011 - 1020
• Main Authors: Michel, Jean–Baptiste, Dussaule, Jean–Claude, Choudat, Laurence, Auzan, Colette, Nochy, Dominique, Corvol, Pierre, Menard, Joel
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.1986; Nature Publishing
• Subjects: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive agents; Applied sciences; Biological and medical sciences; Blood Pressure - drug effects; Body Weight; Cardiovascular system; Clonidine - therapeutic use; Dihydralazine - therapeutic use; Drug Therapy, Combination; Exact sciences and technology; Furosemide - therapeutic use; Hydralazine - analogs & derivatives; Hypertension, Renovascular - drug therapy; Hypertension, Renovascular - pathology; Indoles - therapeutic use; Kidney - pathology; Male; Medical sciences; Organ Size; Other techniques and industries; Perindopril; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Renin - analysis; Renin-Angiotensin System - drug effects; Time Factors; Hypertension; Drug combination; Renal artery; Rat; Rodentia; Enzyme inhibitor; Diuretic; Vertebrata; Renin angiotensin system; Mammalia; Animal; Angiotensin converting enzyme; Antihypertensive agent
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.1986.101

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 undipped 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 undipped 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 undipped kidney. A histological examination revealed that hypertensive microangiopathy was a predominant feature in the undipped 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 undipped 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.