Effects of antihypertensive drugs on blood pressure and metabolic alterations in the fructose-induced hypertensive rat.

Fructose feeding induces a moderate increase in blood pressure (BP) levels in normal rats, which is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. Increased vascular resistances in skeletal muscle have been proposed to contribute to BP elevation and insulin resistance in this animal model. To further explore the mechanisms underlying the fructose-induced hypertension in rats, the effects of quinapril and diltiazem on BP, renal function, plasma levels of glucose, insulin, and triglycerides, and insulin resistance were studied. Male Sprague-Dawley rats were fed for 4 weeks with diets containing 60% fructose or 60% starch and received quinapril or diltiazem in the drinking water. Fructose-fed rats showed higher BP and plasma levels of insulin and triglycerides when compared to controls. Treatments with quinapril or diltiazem prevented BP elevation and reduced elevated plasma insulin levels in fructose-fed rats. Plasma glucose and insulin levels were higher (P < .05) in fructose-fed rats than in controls at 15, 30, and 60 min after oral glucose load. Treatments with either quinapril or diltiazem prevented the exaggerated plasma insulin and glucose levels in response to oral glucose load in fructose-fed rats. In summary, both quinapril and diltiazem were able to prevent BP elevation levels in the fructose-fed rat, and reduced the exaggerated response to an oral glucose tolerance test in these animals.

Acute renal excretory actions of losartan in spontaneously hypertensive rats: role of AT2 receptors, prostaglandins, kinins and nitric oxide.

AIM: The effects of losartan on blood pressure and on renal function have mainly been attributed to AT1 receptor blockade. Experimental evidence suggests that these effects could also be related to the actions of angiotensin II through AT2 receptors or to vasodilatory systems. The present study was therefore designed to investigate the manner in which the acute effects of losartan on renal excretory function are affected during simultaneous administration of an AT2 receptor antagonist, a kinin B2 receptor antagonist, a cyclo-oxygenase inhibitor or a nitric oxide synthesis inhibitor. MATERIALS AND METHODS: The AT2 receptor antagonist PD 123319 (10 mg/kg), the bradykinin B2 receptor antagonist Hoe 140 (30 mu g/kg), the cyclo-oxygenase inhibitor meclofenamate (5 mg/kg) and the nitric oxide synthesis inhibitor NG-monomethyl-L-arginine (1 mu g/kg per min) were administered separately with acute intravenous losartan (1 mg/kg) to spontaneously hypertensive rats and the effects on mean arterial pressure and renal excretory function were assessed. RESULTS: Losartan reduced mean arterial pressure by 11.1 +/- 5.7 mmHg and increased the glomerular filtration rate, urine flow and sodium excretion rate. The decrease in mean arterial pressure was blocked in the presence of NG-monomethyl-L-arginine but not during concurrent administration of PD 123319, Hoe 140 or meclofenamate. The increase in glomerular filtration rate induced by losartan was blunted by Hoe 140, meclofenamate and NG-monomethyl-L-arginine. Co-administration of PD 123319, Hoe 140 or meclofenamate, but not of NG-monomethyl-L-arginine, partially blunted the diuresis and natriuresis induced by losartan. CONCLUSIONS: Nitric oxide participates in the antihypertensive action of losartan. Kinins, prostaglandins and nitric oxide appear to be involved in the effects of losartan on the glomerular filtration rate. The increases in urine flow and sodium excretion rate induced by losartan depend partially on AT2 receptors, kinins and prostaglandins.

Additive antiproteinuric effect of converting enzyme inhibition and a low protein intake.

The hypothesis that converting enzyme inhibition and a protein-restricted diet could have additive antiproteinuric effects has been tested. A group of 17 patients with proteinuria in excess of 3 g/24 h per 1.73 m2 of body surface area were submitted to a 3-wk period of study, after a 4-wk wash-out period during which protein intake was 1.0 g/kg per day and in the absence of any medication. During the first and second weeks of the study, protein intake was lowered to 0.3 g/kg per day, and in the third week, it returned to 1.0 g/kg per day. Enalapril (20 mg daily) was administered during the second and third weeks of the study. Initially and at the end of each week thereafter, we determined blood pressure, GFR (inulin clearance), RPF (para-aminohippurate clearance), plasma sodium and potassium, PRA and aldosterone, and the 24-h urine excretion of sodium potassium, protein, and urea. The low protein intake during the first week induced a significant fall of proteinuria (P < 0.01), GFR (P < 0.01), and RPF (P < 0.01) in the absence of changes in filtration fraction. The addition of enalapril induced a further decrease of proteinuria (P < 0.01) and a fall in filtration fraction (P < 0.05), whereas plasma potassium, PRA, GFR, and RPF values increased (P < 0.01). The rise in protein intake during the last week of the study induced a significant rise in proteinuria, GFR, and RPF (P < 0.01), although the first of these parameters attained values significantly lower (P < 0.05) than those observed initially.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium intake does not influence the effect of verapamil in hypertensive patients with mild renal insufficiency.

Information is limited regarding the efficacy of antihypertensive drugs in patients with hypertension associated with renal insufficiency. To address this question, a group of 14 outpatients with essential hypertension and mild renal insufficiency received slow release verapamil 240 mg/day for 14 days after a 4-week washout period. Patients were randomly assigned to a low (4 g/day) or high (11 g/day) salt diet, and crossed over to the alternative diet after 7 days. 24-Hour blood pressure monitoring was performed at the end of the washout period and after 7 and 14 days during verapamil treatment. Verapamil induced a significant fall in mean 24-hour blood pressure that was similar for patients on both diets (p < 0.01). As expected, natriuresis increased significantly during high sodium intake (p < 0.01), and bodyweight fell significantly when sodium intake was reduced (p < 0.05). Meanwhile, serum creatinine and creatinine clearance remained stable. These results indicate that the antihypertensive effect of verapamil is independent of sodium intake even in the presence of mild renal insufficiency.

Tolerance to nitrendipine in patients with arterial hypertension accompanying chronic renal failure.

To test the tolerance to nitrendipine in arterial hypertension secondary to chronic renal parenchymatous disease, a group of 10 patients so diagnosed and adequately controlled with a diuretic alone or with a beta-blocker were switched to nitrendipine at a dose to insure similarly adequate control of blood pressure. Patients were followed for 1 year at monthly intervals during which blood pressure measurement and the determination of a biochemical profile were performed. During the follow-up, nitrendipine adequately controlled blood pressure and a significant fall was observed in hematocrit (p less than 0.05) and serum uric acid (p less than 0.01) values. Meanwhile, the glomerular filtration rate, determined by the creatinine clearance, did not exhibit significant changes nor did the 24-h urinary excretion of proteins. The tolerance of the drug was adequate, with two patients presenting minimal ankle edema. These results seem to indicate that nitrendipine can be safely used in patients with arterial hypertension secondary to chronic renal parenchymatous disease.