Showing papers by "Luis M. Ruilope published in 1995"

Effects of body-weight loss and captopril treatment on proteinuria associated with obesity.

Abstract: We have identified 17 obese patients (body mass index, BMI, 37.9 ± 4.1)with proteinuria > 1 g/day (1.3-6.4 g/24 h, mean 3.1 ± 1.7). Their age was 34-70 years (48.3 ± 10); 11 were females and 6 males.

Effects of Losartan on Blood Pressure, Metabolic Alterations, and Vascular Reactivity in the Fructose-Induced Hypertensive Rat

Abstract: Fructose feeding induces a moderate increase in blood pressure levels in normal rats that is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. The sympathetic nervous system seems to participate in the alterations of this model. To further explore the mechanisms underlying fructose-induced hypertension, the effects of the AT1 receptor antagonist losartan on blood pressure, insulin resistance, renal function, and vascular reactivity in mesenteric vascular beds were studied. Sprague-Dawley rats were fed for 4 weeks with diets containing 60% fructose or 60% starch (control), and half of each group received losartan (1 mg/kg per day) in the drinking water. Fructose-fed rats showed higher ( P <.05) blood pressure levels and plasma concentrations of triglycerides and insulin than those of controls. Losartan treatment prevented both blood pressure elevation and hyperinsulinemia in fructose-fed rats but not elevation of plasma triglycerides. Plasma glucose and insulin levels in response to an oral glucose load were higher ( P <.05) in fructose-fed rats than in controls. These exaggerated responses were prevented by losartan treatment. No differences in the constrictor responses of mesenteric vascular beds to KCl (60 μmol), angiotensin II (1 nmol), phenylephrine (10−5 mol/L), or endothelin-1 (10 pmol) were found between the two groups. Relaxing responses to acetylcholine or sodium nitroprusside in phenylephrine-precontracted mesenteric vascular beds and constrictor response to the nitric oxide synthesis inhibitor N G-nitro-l-arginine methyl ester (100 nmol) were comparable in both groups. Losartan blunted angiotensin II constriction and reduced ( P <.05) responses to phenylephrine in all groups. In conclusion, these results suggest that angiotensin II plays an important role in the blood pressure elevation and in the insulin resistance induced by fructose feeding in rats. The mechanisms underlying these effects appear to be dependent on neither a vascular hyperreactivity to constrictor factors nor an endothelial dysfunction related to a decreased production of nitric oxide.

Nitric Oxide and Prostaglandins in the Prolonged Effects of Losartan and Ramipril in Hypertension

Abstract: We investigated the role of endogenous nitric oxide, kinins, and prostaglandins in the vasodepressor and renal excretory effects of the angiotensin II receptor antagonist losartan and the angiotensin-converting enzyme inhibitor ramipril administered for 1 week to spontaneously hypertensive rats. To this end, either losartan (10 mg/kg per day) or ramipril (2.5 mg/kg per day) was administered in drinking water with or without simultaneous administration of (1) the nitric oxide synthesis inhibitor N G -nitro-l-arginine methyl ester (L-NAME, 6 mg/kg per day), (2) the cyclooxygenase inhibitor indomethacin (5 mg/kg per day), (3) the bradykinin B 2 receptor antagonist Hoe 140 (0.5 mg/kg per day SC), or (4) L-NAME plus indomethacin. Both losartan and ramipril significantly reduced blood pressure as measured by the tail-cuff method. L-NAME increased blood pressure when administered solely or in combination with losartan. However, L-NAME attenuated the hypotensive effect of ramipril. Indomethacin did not affect blood pressure but it reduced the antihypertensive action of losartan and ramipril. Indomethacin administration did not potentiate the increase in blood pressure induced by L-NAME. However, the concurrent administration of both inhibitors almost totally blunted the vasodepressor action of ramipril. By contrast, losartan administration in the presence of L-NAME and indomethacin increased blood pressure to a level similar to that after losartan plus L-NAME. Hoe 140 did not modify either blood pressure or the hypotensive effects of losartan or ramipril. Increases in diuresis and water intake were observed during ramipril administration. Both effects were blunted only with the concurrent administration of L-NAME and indomethacin. None of the cotreatments were able to modify renal excretory function by themselves. These data suggest a contribution of endogenous nitric oxide and prostaglandins but not of kinins in the prolonged antihypertensive effect of both losartan and ramipril in the spontaneously hypertensive rat.

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

Abstract: Aim : The effects of losartan on blood pressure and on renal function have mainly been attributed to AT 1 receptor blockade. Experimental evidence suggests that these effects could also be related to the actions of angiotensin II through AT 2 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 AT 2 receptor antagonist, a kinin B 2 receptor antagonist, a cyclo-oxygenase inhibitor or a nitric oxide synthesis inhibitor. Materials and methods : The AT 2 receptor antagonist PD123319 (10 mg/kg), the bradykinin B 2 receptor antagonist Hoe 140 (30 μg/kg), the cyclo-oxygenase inhibitor meclofenamate (5 mg/kg) and the nitric oxide synthesis inhibitor N G -monomethyl-L-arginine (1 μg/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 N G -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 14o, meclofenamate and N G -monomethyl-L-arginine. Co-administration of PD123319, Hoe 140 or meclofenamate, but not of N G -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 AT 2 receptors, kinins and prostaglandins.

Assessing renal effects and renal protection.

Abstract: ASSESSMENT OF RENAL FUNCTION: There are a number of methods of evaluating renal function, including measurements of glomerular filtration, renal plasma flow, tubular function, micro- and macroalbuminuria and urinary sediment. Of these, microalbuminuria, glomerular filtration and renal plasma flow are the most appropriate. RENAL EFFECTS OF CALCIUM ANTAGONISTS: Calcium antagonists have important effects on renal function, including a reduction in renal vasoconstriction, increased renal blood flow and, in some circumstances, reduced protein excretion. In particular, these agents can reverse the mild renal vasoconstriction that is seen in the offspring of hypertensive patients. The renal effects of calcium antagonists have been studied in animal models, where radioimaging techniques have shown a biphasic haemodynamic response. RENAL PROTECTION WITH CALCIUM ANTAGONISTS: Two important beneficial effects of calcium antagonists are prevention of acute renal failure and protection against cyclosporin nephrotoxicity. Calcium antagonists have thus been used therapeutically in renal transplant patients and in patients with acute renal failure secondary to the effects of nephrotoxic agents.

Antihypertensive Treatment Efficacy in Type II Diabetes Mellitus Dissociation Between Casual and 24-Hour Ambulatory Blood Pressure

Abstract: Whole-day ambulatory blood pressure monitoring is used to confirm the diagnosis of hypertension and assess the response to antihypertensive therapy. Neither of these has been applied to patients with type II diabetes mellitus, in whom it has been proposed that the desirable blood pressure should be lower than in nondiabetics. This multicenter study was designed to examine whether there are differences in the efficacy of a first-line antihypertensive drug when assessed by casual and ambulatory blood pressure determinations in patients with type II diabetes mellitus in whom 24-hour ambulatory monitoring confirms or fails to confirm the diagnosis of hypertension. Forty-three patients (mean age, 57.7 years) with stable type II diabetes mellitus and mild hypertension (casual diastolic pressure, 90 to 104 mm Hg on at least two visits) were treated with an angiotensin-converting enzyme inhibitor (benazepril, 10 to 20 mg, once a day) for 8 weeks. Antihypertensive drug efficacy was assessed by casual (trough) and 24-hour ambulatory blood pressure monitoring. Diabetic patients were classified as nonconfirmed hypertensive if the mean 24-hour ambulatory diastolic pressure was below 85 mm Hg. Antihypertensive treatment significantly decreased both systolic and diastolic pressures when determined by either casual measurement (from a mean of 162.7/98.0 to 153.9/89.2 mm Hg; P < .001) or ambulatory monitoring (from a mean of 143.1/84.4 to 137.0/81.5 mm Hg; P < .05). Twenty-one patients (49%) were classified as confirmed hypertensive and 22 as nonconfirmed hypertensive. In confirmed hypertensive patients benazepril significantly reduced systolic and diastolic pressures when assessed by either casual or 24-hour ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of angiotensin converting enzyme inhibitors on the progression of diabetic nephropathy

Abstract: Aim To review recent studies on the effect of angiotensin converting enzyme (ACE) inhibitors on diabetic nephropathy. Method Literature review. Results Strict glucose control, a low protein intake and aggressive blood pressure control are the main requirements for the preservation of renal function in patients with diabetes mellitus. Recent work has shown that ACE inhibitors have renoprotective actions in diabetes that go beyond their capacity to lower blood pressure. Through these actions they slow the progression of renal failure and prevent the development of macroalbuminuria that characterizes the onset of diabetic nephropathy. Conclusions ACE inhibitors may be considered the drugs of choice in diabetic patients with either hypertension or some degree of renal dysfunction.

The hidden truth: what do the clinical trials really tell us about BP control?

Abstract: Prospective observational studies show clearly that the risks of stroke, coronary heart disease and premature death are related directly to BP. Furthermore, the results of prospective, randomised intervention studies indicate that effective BP control reduces these risks. Although the number of patients being treated for hypertension has approximately doubled in the last 20 years, premature morbidity and mortality remain higher than in the normotensive population. This may relate to the inadequate level of BP control achieved in many patients. Two large studies have shown that DBP can be reduced to < 90 mmHg in almost all patients if antihypertensive therapy is intensified, and preliminary evidence suggests that this can be done without increasing the incidence of side-effects. The level to which BP should be reduced to achieve an optimum reduction in cardiovascular morbidity and mortality is currently being investigated in the Hypertension Optimal Treatment (HOT) Study.

Renal damage in hypertension.

Abstract: The kidney can be considered as both culprit and victim in the hypertensive process. Deranged renal function contributes to the development of arterial hypertension and of secondary vascular damage at the glomerular and arteriolar level and accounts for the development of progressive nephrosclerosis. The most common alteration of renal function observed in humans from the early stages of essential hypertension is the presence of renal vasoconstriction. This can be accompanied by hyperuricaemia and increased urinary excretion of enzymes such as N-acetyl-beta-glucosaminidase and proteins such as albumin and beta 2-microglobulin. Later, a progressive fall in glomerular filtration rate, sometimes accompanied by proteinuria, can be observed if high blood pressure persists.