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Biomedical subjects

L M Ruilope

Publications and source records attributed to L M Ruilope.

At least 127 records · Page 7Linked to original sources
PubMed1995

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.

Adrenergic beta-Antagonists↗
PubMed1994

Comparison of a new vasodilating beta-blocker, carvedilol, with atenolol in the treatment of mild to moderate essential hypertension.

Carvedilol is a new cardiovascular compound with the combined pharmacologic properties of nonselective beta-blockade and vasodilation. The aim of this study was to compare the safety and antihypertensive efficacy of 25 to 50 mg carvedilol once daily with 50 to 100 mg atenolol once daily in patients with mild to moderate essential hypertension. This was a multicenter study conducted in Europe. After a single-blind placebo run-in phase, 325 eligible patients with stable hypertension were randomized to receive 25 mg carvedilol once daily (161 patients) or 50 mg atenolol (164 patients) in a double-blind 8-week treatment phase. After 4 weeks, the dosage was doubled if there was inadequate response. The primary index of efficacy (response) was the reduction of mean sitting diastolic blood pressure to 90 mg Hg or less (normalized) or by at least 10 mm Hg from baseline. At each of three to six run-in phase visits and after 2, 4, and 8 weeks of treatment, sitting blood pressure and heart rate at trough were measured in triplicate, and body weight, adverse experiences, compliance, and use of concomitant medications were assessed. Laboratory tests, including fasting serum lipids, and electrocardiograms were also monitored during the trial. After 8 weeks of treatment, response rates in the carvedilol and atenolol treatment groups were 75% and 82%, respectively. Compared to baseline, the mean sitting blood pressure was significantly (P < .05) reduced by carvedilol from 165/104 mm Hg to 147/89 mm Hg. With atenolol, mean sitting blood pressure was significantly (P < .05) reduced from 167/104 mm Hg to 150/90 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Evaluation of the renal effects of calcium antagonists.

Calcium antagonists exert renal effects consisting mainly of renal vasodilation and facilitation of renal excretion of sodium through a direct action on renal tubules. These effects facilitate the antihypertensive action of this class of drugs and make them suitable for therapy of different forms of human hypertension, including that accompanying chronic renal failure. At the same time, renal vasodilation and enhanced natriuresis could also be of value for correcting the renal defect that initiates essential hypertension. Renal effects of calcium antagonists have also fostered the concept of a renoprotective effect of these drugs in different situations. A demonstration of this concept has been shown in cyclosporine-related nephrotoxicity. Calcium antagonists can improve the short- and long-term prognosis for renal function in human transplantation through their effects in avoiding cyclosporine-induced renal vasoconstriction and in facilitating renal sodium output.

Antihypertensive Agents↗
PubMed1994

Hormonal, renal, and metabolic alterations during hypertension induced by chronic inhibition of NO in rats.

The evolution of renal excretory function and circulating vasoactive systems was studied during progressive increases in blood pressure (BP) induced in rats by oral administration of NG-nitro-L-arginine methyl ester (L-NAME; 5-30 mg/100 ml) for 5 wk. L-NAME induced a stepped elevation (P < 0.05) in BP levels without changing creatinine clearance, urine flow, or sodium excretion rate along the study. Reductions (P < 0.05) in plasma renin activity and plasma aldosterone concentration were found only during treatment with 30 mg/100 ml of L-NAME. Plasma norepinephrine and epinephrine concentrations were elevated (P < 0.05) in the last week of the study. Plasma concentrations of endothelin-1 and urinary excretion of prostaglandin E2, 6-ketoprostaglandin F1 alpha, and thromboxane B2 were not significantly affected by L-NAME. Similarly, no changes in plasma concentrations of glucose, insulin, total cholesterol, or triglycerides were observed. In summary, during long-term administration of L-NAME, progressive increases in BP levels were observed without changes in either sodium excretion or enhanced circulating vasoconstrictor activity. Thus, it is likely that inhibition of synthesis of nitric oxide (NO) in the vasculature leads to an imbalance between the tonic relaxing action of NO and the influences of vasoconstrictor agents even when the latter remain at normal levels.

Aldosterone↗
PubMed1994

Are renal hemodynamics a key factor in the development and maintenance of arterial hypertension in humans?

The kidney plays a key role in the control of body fluids and blood pressure. Evidence has shown that impairment of renal function can lead to the development of arterial hypertension. The regulation of renal blood flow appears to be a key element in the pathophysiology of the hypertensive process, because multiple evidence suggests the existence of a functional enhancement of renal vascular tone in this disorder. The existence of renal vasoconstriction and of an inherited defect in the regulation of renal blood flow has been proposed in the prehypertensive stage. The mechanisms responsible for this alteration include a lack of modulation of the renal vasculature to angiotensin II, increased sympathetic activity, or suppressed renal dopaminergic activity. Established hypertension is characterized by elevated renal vascular resistance, decreased renal blood flow, sustained glomerular filtration rate, and increased filtration fraction. The increase in renal vascular resistance is initially due to elevations in renal vascular tone and is reversible, whereas later it becomes irreversible because of structural changes involved in nephrosclerosis. Antihypertensive drugs are able to decrease blood pressure and to prevent the development of further renal vascular damage independently of variable effects on renal hemodynamics.

Antihypertensive Agents↗
PubMed1994

How much does the kidney participate in the origin of primary hypertension?

The existence of a relationship between the kidney and arterial hypertension has long been known. Renal participation in the development of arterial hypertension has been clearly shown in different animal models that mimic human essential hypertension. Different theories have tried to explain the mechanism(s) underlying the renal participation in human hypertension. According to the data contained in the literature renal vasoconstriction is present in the kidney since the very early stages of the hypertensive disease and could constitute the mechanism facilitating the development of arterial hypertension.

Animals↗
PubMed1994

Relationship between blood pressure and renal function.

RENAL DAMAGE CAUSED BY HYPERTENSION: Renal vasoconstriction seems to be a key factor in the origin of arterial hypertension and accounts for the decrease in renal blood flow commonly observed in patients with hypertension. An inverse correlation has been found between renal blood flow and clinic blood pressure levels in established hypertension. Other features of renal damage attributable to high blood pressure have also been correlated with clinic blood pressure levels. Microalbuminuria is a good example of an alteration in renal function that depends in part on blood pressure levels. EFFECTS OF ANTIHYPERTENSIVE AGENTS: Antihypertensive agents can prevent or ameliorate renal vascular damage secondary to arterial hypertension, including renal failure. Ambulatory blood pressure monitoring is an excellent method of studying blood pressure levels in relation to end-organ damage and the blood pressure response to antihypertensive agents. Preliminary studies using this technique indicate that changes in renal function are closely correlated with the average daily blood pressure in arterial hypertension. CONCLUSIONS: Further studies are needed on the mechanisms of renal deterioration and on how to preserve renal function in arterial hypertension.

Antihypertensive Agents↗
PubMed1994

Randomly allocated study of the effects of standard therapy versus ACE inhibition on micro-albuminuria in essential hypertension.

OBJECTIVE: To compare the effects of standard therapy (diuretic, beta-blocker or both) with those of angiotensin converting enzyme (ACE) inhibition with quinapril on renal function and urinary albumin excretion in patients with essential hypertension. METHODS: A 1-year, placebo-controlled, randomly allocated study was conducted in a group of 40 patients with essential hypertension. Before beginning the active treatment phase, all patients were given a matched placebo for quinapril for at least 14 days. At baseline and after 1, 3, 6 and 12 months of treatment, blood pressure, heart rate, body weight, renal plasma flow, glomerular filtration rate, plasma renin activity, plasma aldosterone and urinary albumin excretion were measured. RESULTS: Both the standard therapy and quinapril produced similar decreases in blood pressure, but only quinapril produced a significant decrease in micro-albuminuria, from 68.5 +/- 16.7 to 47.2 +/- 14.9 mg/24 h (P < 0.05). The renal plasma flow remained constant in both study groups while the glomerular filtration rate and filtration fraction decreased significantly (P < 0.05) in the quinapril group. CONCLUSIONS: The results of this study indicate that long-term therapy for essential hypertension with ACE inhibition has a more favorable effect on micro-albuminuria than standard therapy for an equal level of blood pressure control.

Adrenergic beta-Antagonists↗
PubMed1994

Electrolyte excretion and sodium intake.

Established essential hypertension is characterized by normal equilibrium between the intake and renal excretion of sodium. Urinary sodium excretion is interrelated with that of other ions, such as potassium and calcium, and that the response of blood pressure to salt ingestion can be conditioned by the simultaneous intake of varying levels of those ions. The authors address three aspects: the correlations between urinary excretion of sodium and calcium and sodium and potassium in a population of untreated essential hypertensive persons, the response of blood pressure during the escape induced by exogenous mineralocorticoid administration in mild essential hypertension, and the effect of intravenous calcium gluconate infusion on sodium excretion and renal function. The first part shows that sodium excretion is closely correlated with that of other ions in essential hypertension, and the second part shows that, to escape from the sodium-retaining effect of a mineralocorticoid, mild hypertensive subjects must have increased blood pressure within or near the cutoff point that defines salt sensitivity. Of interest, the elevation in blood pressure takes place while sympathetic nervous activity is blunted. The third part provides evidence to explain one of the mechanisms by which calcium influences renal function and enhances renal sodium excretion. The intrarenal effects of low doses of calcium are dependent on the renal production of prostaglandins.

Atrial Natriuretic Factor↗
PubMed1993

Effects of captopril on sympathetic activity, lipid and carbohydrate metabolism in a model of obesity-induced hypertension in dogs.

Ten age-matched beagle dogs were kept on a high-fat diet and followed for 12 weeks. During this period the animals were divided into two groups (n = 5), either with or without oral captopril treatment. Dogs were tested periodically for biochemical and clinical parameters, and at the end of the study animals were killed and thoracic aorta samples were obtained for histologic evaluation. From the third week, the captopril group presented significantly lower values of mean arterial pressure, plasma norepinephrine, and fasting glucose and cholesterol levels than those attained in the nontreated group. Furthermore, aorta samples from untreated animals showed profuse staining for fat content at the intima and adventitia layers, while this reaction was restricted to the outer layer in treated dogs. These data suggest that the beneficial effects of captopril therapy in this obesity-induced hypertension model could be based on blood pressure control, together with reduction of serum glucose, cholesterol, and sympathetic activity levels. In addition, captopril treatment could play a role in the retardation of the early stages of vascular atherogenetic lesion.

Animals↗
PubMed1993

Cicaprost, a prostacyclin analog, protects renal function in uninephrectomized dogs in the absence of changes in blood pressure.

Ten dogs presenting mild chronic renal failure and hypertension after 27 months of uninephrectomy, during which they received a high sodium and high protein diet, were divided in two groups (n = 5) and followed for 15 months. The same diet was maintained and one of the groups received cicaprost treatment. The animals were periodically tested for biochemical and clinical parameters, and at months 0, 3, 6, and 15, glomerular filtration rate and renal plasma flow (RPF) were measured. Renal biopsies were made after 6 months of follow-up. Control group showed a higher thickening of pre- and intraglomerular portions of arteriolar vessels and an enhancement of mesangial matrix when compared with the treated group. Cicaprost also induced a significant elevation in RPF and a significant decrease in filtration fraction. All these findings suggest that cicaprost, an oral stable prostaglandin I2 analog, could have a protective renal effect in this experimental model.

Animals↗
PubMed1993

Calcium antagonists and renal protection.

AIM: To review the renal benefits of calcium antagonists. METHODS: Review of published studies. RESULTS: Both experimental and clinical studies have indicated that, apart from being highly potent antihypertensive agents, calcium antagonists may also provide tissue protection and preservation. In three well defined clinical situations, the use of calcium antagonists has proved to be of value. First, in acute renal failure we and others have shown that the administration of dihydropyridine or diltiazem can, by preventing an intracellular calcium overload, avoid the renal damage induced by the use of a radiographic contrast agent. Second, in chronic renal failure, the administration of a calcium antagonist has been shown to be safe and at least similar in efficacy to other commonly used antihypertensive drug classes. Third, in renal transplant patients, calcium antagonists have been shown to prevent both acute and chronic cyclosporin nephrotoxicity. Calcium antagonists have a clear advantage in the case of acute toxicity because they allow faster renal function recovery and a shorter hospitalization time. The mechanisms by which this class reduces cyclosporin toxicity may be related to a reduction in the calcium influx into cells during ischaemic and reperfusion periods, which would reduce the generation of oxygen-free radicals and perhaps reduce thromboxane production. CONCLUSIONS: Calcium antagonists have potential renal protective effects that favour their use in many clinical situations where renal function is impaired.

Animals↗