Showing papers by "Luis M. Ruilope published in 1993"

Calcium antagonists and renal protection.

Abstract: 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.

Clinical relevance of proteinuria and microalbuminuria.

Abstract: Proteinuria (protein excretion > 300 mg/d) is an independent risk factor for the development of cardiovascular disease and renal failure The finding of persistent proteinuria in otherwise asymptomatic patients often precedes the development of arterial hypertension and renal failure When proteinuria is accompanied by arterial hypertension, blood pressure control can decrease the quantity of protein excretion but not the incidence of proteinuria In this sense, converting enzyme inhibitors seem to possess a higher capacity to reduce proteinuria Nevertheless, the effects of reducing proteinuria on renal function and cardiovascular risk remain to be elucidated Microalbuminuria (urine albumin excretion oscillating between 30 and 300 mg/d) seems to be a predictor of cardiovascular disease in diabetic and nondiabetic subjects and has been established as a predictor for the development of diabetic nephropathy Blood pressure levels and urinary albumin excretion correlate positively, and antihypertensive therapy of any kind decreases the quantity of albumin present in the urine The role of increased albumin excretion in essential hypertension and in renal failure remains to be elucidated

Exogenous cGMP prevents decrease in diuresis and natriuresis induced by inhibition of NO synthesis

Abstract: We previously demonstrated that the intravenous infusion of the specific inhibitor of nitric oxide (NO) synthesis, NG-nitro-L-arginine methyl ester (L-NAME), over a period of 60 min elevates mean arterial pressure (MAP) and reduces renal hemodynamics and excretory function. The objective of the present study was to determine the ability of a guanosine 3',5'-cyclic monophosphate (cGMP) analogue, 8-bromo-cGMP (8-BrcGMP), in preventing the increase in MAP and the reductions in renal plasma flow (RPF), glomerular filtration rate (GFR), urine flow (UV), and sodium excretion rate (UNaV) induced by intravenous infusion of L-NAME in rats. As expected, the infusion of L-NAME (50 micrograms.kg-1.min-1) increased (P < 0.05) MAP and reduced (P < 0.05) RPF, GFR, UV, and UNaV. The administration of 8-BrcGMP (100 micrograms.kg-1.min-1) and L-NAME resulted in no change in MAP, RPF, and GFR. However, decreased (P < 0.05) UV and UNaV were still observed. When 8-BrcGMP (200 micrograms.kg-1.min-1) and L-NAME were infused together, no significant changes in MAP or in renal function were observed. To prove the specificity of the 8-BrcGMP preventive effects, dibutyryl cAMP (200 micrograms.kg-1.min-1) and L-NAME (50 micrograms.kg-1.min-1) were infused together. Under these conditions, MAP, RPF, GFR, UV, and UNaV were modified in a manner similar to that observed during the infusion of L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive effect of nitrendipine in the hypertensive patient with renal impairment

Abstract: Calcium antagonists exert several characteristic effects on the kidney that potentiate their antihypertensive effect. The objective of the present study was to investigate the effectiveness of nitrendipine in the presence of different degrees of renal impairment. Two groups of hypertensive patients were included in the study. Group 1:10 patients with arterial hypertension secondary to chronic renal parenchymatous disease and adequately controlled with a diuretic and/or a beta-blocker who were switched to nitrendipine. These patients were then followed monthly for 1 year. Group 2:24 patients diagnosed as having essential hypertension who presented values of urinary albumin excretion above 30 mg/day after a minimum of 3 years of adequate blood pressure control with a diuretic and/or a beta-blocker. Patients were randomly assigned to continue with the same therapy or to switch to nitrendipine for 1 year. In both groups nitrendipine was as efficacious as standard therapy for controlling blood pressure and did not induce changes in renal hemodynamics. Nitrendipine did not modify the level of proteinuria in group 1, nor the urinary excretion of albumin in group 2. These results seem to indicate that nitrendipine can be safely used in patients with arterial hypertension and different degrees of renal function impairment.

Influence of salt intake on the antihypertensive effect of carvedilol

Abstract: AIM To investigate whether moderate sodium restriction can increase the proven antihypertensive effect of carvedilol, a newly developed beta-blocker with vasodilating properties. METHOD A randomly allocated double-blind crossover in 19 patients. RESULTS Lowering dietary salt increased the fall in blood pressure obtained with carvedilol.

Lipophilic dihydropyridines provide renal protection from cyclosporin toxicity.

Abstract: Aim To review cyclosporin nephrotoxicity and its prevention by calcium antagonists. Method Review of published and unpublished studies. Results Cyclosporin A nephrotoxicity is the most important side effect of this potent immunosuppressive drug. Several mechanisms have been implicated in the production of this adverse effect but elevated endothelin release is perhaps the most frequently cited cause. Calcium antagonists have demonstrated a beneficial effect in preventing cyclosporin A nephrotoxicity in renal cadaveric transplants, during both short- and long-term follow-up. Lacidipine, a lipophilic dihydropyridine calcium antagonist, prevents the reductions in the glomerular filtration rate and renal plasma flow that are often seen after cyclosporin A administration. This effect is not related to endothelin suppression. Conclusions Calcium antagonists can provide renal protection in patients who undergo renal cadaveric transplantation and are treated with cyclosporin.

Angiotensin-converting enzyme inhibitors in the treatment of mild arterial hypertension.

Abstract: Angiotensin-converting enzyme inhibitors are nowadays widely employed for the treatment of arterial hypertension. They exhibit comparable levels of efficacy and better tolerability when compared with the other antihypertensive agents. In mild arterial hypertension they have been shown to be more efficacious than nonpharmacological therapy that is recommended as the first-step therapeutic approach for most cases of this type of hypertension. Potential advantages for the control of associated metabolic risk factors and specific renal and cardiac effects make these drugs suitable for the first step pharmacological therapy on mild hypertension.

The Kidney and Arterial Hypertension

Abstract: It has been known for some time that a relationship exists between the kidney and blood pressure. The renal origin of arterial hypertension has been demonstrated in different animal models resembling human hypertension, with data from humans seeming to confirm this hypothesis. On the other hand, the renal vasculature also suffers the consequences of arterial hypertension, and renal insufficiency can develop as a result of elevated blood pressure levels. Antihypertensive therapy can prevent the development of renal damage secondary to hypertension. For example, calcium antagonists possess specific renal effects that not only facilitate their antihypertensive capacity but also protect the kidney from the development of renal failure.

Natriuretic effects of dopamine agonist drugs in models of reduced renal mass.

Abstract: In addition to recognized neurotransmitter properties in the central nervous system, dopamine (DA) plays a role in the physiological activity of the kidney through its hemodynamic and natriuretic effects. On the basis of these data, some pharmacological interventions have focused their attention on the use of DA-related drugs to improve renal sodium handling. We summarize the data obtained from two studies using two DA agonist drugs, lisuride (LIS) and fenoldopam (FEN), in two situations of reduced renal mass. During an intravenous sodium load performed on 10 uninephrectomized dogs, LIS induced a significant blockade of the concomitant pressor response, estimated by lower blood pressure and norepinephrine levels

Kidney and aetiology, pathology and management of essential hypertension.

Abstract: 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. Some data obtained in hypertensive humans also seem to support the prevalence of the kidney in the initiation of this particular type of arterial hypertension. On the other hand, renal vasculature can also suffer the consequences of essential hypertension and, as a result, chronic renal failure can develop. The role of antihypertensive therapy in preventing renal damage has been sufficiently addressed. However, investigation of the potential for facilitating the antihypertensive capacity of drugs through their renal effects and investigation of the differing abilities of particular groups of antihypertensive agents to prevent or slow the progression of renal damage constitutes a challenge for future research.