Chronic administration of rGLP-1 significantly attenuated the development of hypertension in Dahl salt-sensitive rats (136 vs 174 mmHg) and reduced proteinuria and albuminuria.
Does rGLP-1 reduce mean arterial pressure and end-organ damage in Dahl salt-sensitive rats on a high salt diet?
rGLP-1 attenuates hypertension and provides cardiac and renoprotective effects in Dahl salt-sensitive rats on a high salt diet, primarily through diuretic and natriuretic mechanisms.
Absolute Event Rate: 136% vs 174%
BACKGROUND: Dahl salt-sensitive (Dahl S) rats exhibit many phenotypic traits associated with salt-sensitive hypertension in man. Specifically, they are salt-sensitive, insulin-resistant and hyperlipidemic. They also develop endothelial dysfunction, cardiac injury and glomerulosclerosis. Insulin resistance is linked to hypertension, renal and cardiac damage and endothelial dysfunction. Thus, an agent that has diuretic action and can improve insulin resistance, like recombinant glucagon-like peptide-1(7-36)amide (rGLP-1), may have an antihypertensive effect. OBJECTIVE: To determine whether chronic administration of rGLP-1 attenuates the development of hypertension, endothelial dysfunction and/or hypertension-induced renal and cardiac end organ damage in Dahl S rats. METHODS: Mean arterial pressure (MAP) and urinary excretion of protein and albumin were measured in Dahl S rats before and after they were fed a 8% NaCl diet and infused with rGLP-1 (1 micro g/kg per min, i.v.) or vehicle for 14 days. At the end of the study, the degree of renal and cardiac injury was histologically assessed and endothelium-dependent relaxing function was studied using aortic rings. In other rats, the effects of rGLP-1 on sodium and water balance and plasma glucose and insulin levels for the first 3 days following a step change in sodium intake from a 0.1% NaCl diet to 7.5 mEq/day were determined. RESULTS: rGLP-1 significantly attenuated the development of hypertension in Dahl S rats (136 +/- 7 versus 174 +/- 6 mmHg). This was associated with reduction in proteinuria (46 +/- 7 versus 128 +/- 15 mg/day) and albuminuria (46 +/- 7 versus 86 +/- 18 mg/day) and improvement of endothelial function and renal and cardiac damage. rGLP-1 markedly increased urine flow and sodium excretion for the first 3 days following elevation in sodium intake. It had no significant effects on plasma glucose and insulin concentrations. CONCLUSION: rGLP-1 has antihypertensive and cardiac and renoprotective effects in Dahl S rats fed a high salt diet. The antihypertensive effect of rGLP-1 in Dahl S rats is due mainly to its diuretic and natriuretic effects, rather than an effect to improve insulin-resistance.
Yu et al. (Sat,) conducted a other in Salt-sensitive hypertension. recombinant glucagon-like peptide-1(7-36)amide (rGLP-1) vs. vehicle was evaluated on Mean arterial pressure (MAP). Chronic administration of rGLP-1 significantly attenuated the development of hypertension in Dahl salt-sensitive rats (136 vs 174 mmHg) and reduced proteinuria and albuminuria.
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