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J Hypertens. 1995 Apr;13(4):439-45.
Sympathetic nerve activity in conscious renal hypertensive rats treated with an angiotensin converting enzyme inhibitor or an angiotensin II antagonist.

Niederberger M, Aubert JF, Nussberger J, Brunner HR, Waeber B.

Division of Hypertension, University Hospital, Lausanne, Switzerland.

OBJECTIVE: To assess in conscious two-kidney, one clip renal hypertensive rats whether angiotensin converting enzyme (ACE) inhibition with lisinopril, angiotensin II receptor blockade with losartan or vasodilation with sodium nitroprusside have similar effects on intra-arterial mean blood pressure, heart rate and splanchnic nerve activity. RESULTS: A bolus dose of lisinopril or losartan (both 10 mg/kg, intravenously) induced within 2 h an equal reduction in mean blood pressure, whereas sodium nitroprusside infused during the same period (at 10 micrograms/min) lowered mean blood pressure, but less strongly. The heart rate was accelerated significantly more during sodium nitroprusside infusion than during lisinopril or losartan treatment. Splanchnic nerve activity increased significantly only in those rats given sodium nitroprusside. No change in the parameters studied was observed in vehicle-treated rats. The doses of lisinopril and losartan were repeated after 12 and 24 h. Before administration of the last dose, the mean blood pressure was still low. Administration of lisinopril or losartan again 24 h after the initial dose had no further effect on the mean blood pressure, heart rate or splanchnic nerve activity. CONCLUSION: These results obtained in rats with a renin-dependent form of hypertension show that blockade of the renin-angiotensin system for 24 h produces an equivalent blood pressure reduction irrespective of whether it is due to ACE inhibition or angiotensin II antagonism. The results also indicate that there is less reflex activation of sympathetic nerve activity when blood pressure is lowered with a blocker of the renin-angiotensin system rather than with a direct vasodilator such as sodium nitroprusside.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7629405&dopt=Abstract

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Hypertension. 1995 Aug;26(2):321-6.
Contribution of systemic blood pressure to myocardial remodeling in uremic rats.

Fabris B, Carretta R, Fischetti F, Candido R, Calci M, Castellano M, Bardelli M, Campanacci L.

Institute of Medicina Clinica, Cattinara Hospital, University of Trieste, Italy.

Left ventricular hypertrophy with diffuse intermyocardiocytic fibrosis is a feature of uremia. The role of blood pressure and/or other cardiovascular uremic risk factors in cardiac remodeling is still uncertain. To determine the extent to which improvement of kidney function and the control of uremia-related risk factors are associated with a reduction of myocardial injury, we evaluated the effect of dietary protein restriction or the angiotensin-converting enzyme inhibitor lisinopril on cardiac structure in remnant kidney rats. One week after subtotal nephrectomy, Wistar rats were allocated to receive drinking water solution (group 1), 5 mg/kg per day lisinopril (group 2), or a low-protein diet (6%) (group 3) for 12 weeks. Group 2 and 3 showed a comparable efficacy in preventing the expected rise in creatininemia, urinary protein excretion, and glomerulosclerosis. However, hypertension development was prevented only in group 2. Groups 1 and 3 developed a significant (P < .01) increase in left ventricular weight (2.45 +/- 0.1 and 2.5 +/- 0.5 mg/g body wt, respectively) compared with group 2 (1.9 +/- 0.06 mg/g body wt). Cardiac hydroxyporline concentration was also lower in group 2 compared with group 1 (2.07 +/- 0.16 versus 2.73 +/- 0.17 mg/g left ventricular weight, P < .05) but not compared with group 3 (2.59 +/- 0.19 mg/g left ventricular weight). The effect of angiotensin-converting enzyme inhibition on left ventricular mass and intracardiac collagen content appeared to be dissociated from anemia, sympathetic activity, and hyperlipidemia. There was a close relationship between systolic pressure and left ventricular mass; however, no relationship between the degree of cardiac fibrosis and systolic pressure could be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7635542&dopt=Abstract

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Kidney Int. 1995 May;47(5):1319-26.
ACE inhibition prevents renal failure and death in uninephrectomized MWF/Ztm rats.

Remuzzi A, Benigni A, Malanchini B, Bruzzi I, Foglieni C, Remuzzi G.

Mario Negri Institute for Pharmacological Research, Bergamo, Italy.

Many studies have consistently documented that angiotensin converting enzyme (ACE) inhibitors prevent proteinuria and glomerulosclerosis in progressive renal disease, but very few data are available on whether they also prevent renal failure and death. The mechanisms of the beneficial effect of ACE inhibition are only partially understood. Recent data suggest that angiotensin II modulates renal synthesis of endothelin-1, a vasoactive peptide implicated in the process of renal injury. Here we investigated in a long-term study whether ACE inhibition ameliorated renal function in uninephrectomized (UNx) male MWF/Ztm rats. Three groups of rats at nine weeks of age underwent UNx or sham-operation. Nephrectomized animals were left untreated or treated with the ACE inhibitor lisinopril in drinking water. In untreated UNx animals systolic blood pressure, serum creatinine, urinary protein and renal synthesis of endothelin-1, evaluated by its urinary excretion, were significantly increased, as compared with control animals with two kidneys. End-stage renal failure developed in all untreated UNx rats that died within 9 to 14 months from UNx. ACE inhibitor significantly reduced systolic blood pressure, completely prevented proteinuria and renal function deterioration, and reduced endothelin-1 excretion. All UNx rats treated with lisinopril were alive 14 months after UNx. These results show that ACE inhibition prevents end-stage renal failure induced by UNx in male MWF/Ztm, and that the beneficial effects of angiotensin II inhibition in this model are related to modulation of renal synthesis of endothelin-1.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7637261&dopt=Abstract

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