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Biomedical subjects

V Lahera

Publications and source records attributed to V Lahera.

At least 55 records · Page 3Linked to original sources
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

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

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

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)

Animals↗
PubMed1993

Sulfhydryl group donors potentiate the hypotensive effect of acetylcholine in rats.

Nitric oxide mediates the vasodilator and hypotensive responses of acetylcholine infusion. It has been reported that nitric oxide could be protected from free radical destruction by forming an S-nitrosothiol compound. Furthermore, sulfhydryl donors such as N-acetylcysteine or thiosalicylic acid enhance nitric oxide production from nitroglycerin. Consequently, the hypotensive effect of intravenous acetylcholine infusion might be potentiated during the simultaneous administration of sulfhydryl donors. The objective of the present study was to test in Okamoto spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (1) whether the hypotensive effect of acetylcholine (10 micrograms/kg per minute) was affected by the simultaneous administration of N-acetylcysteine (10 micrograms/kg per minute) or thiosalicylic acid (10 micrograms/kg per minute), and (2) whether NG-nitro-L-arginine-methyl ester (100 micrograms/kg per minute) administration was able to reverse the changes induced by acetylcholine plus N-acetylcysteine or acetylcholine plus thiosalicylic acid. The administration of acetylcholine reduced (P < .05) mean arterial pressure in WKY rats (13 +/- 2%) and SHR (14 +/- 2%) without affecting urine flow rate, urinary sodium excretion, and glomerular filtration rate. In the presence of N-acetylcysteine, the acetylcholine-induced reduction in mean arterial pressure was potentiated (P < .05) in WKY rats (24 +/- 4%) and SHR (20 +/- 2%). These changes in mean arterial pressure were accompanied by significant reductions in urine flow rate and urinary sodium excretion in WKY rats, as well as in glomerular filtration rate in SHR.2

Acetylcholine↗
PubMed1993

The kidney and arterial hypertension.

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.

Animals↗
PubMed1993

Antihypertensive effect of nitrendipine in the hypertensive patient with renal impairment.

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.

Adult↗
PubMed1993

Influence of salt intake on the antihypertensive effect of carvedilol.

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.

Adrenergic beta-Antagonists↗
PubMed1992

Blockade of pressure natriuresis induced by inhibition of renal synthesis of nitric oxide in dogs.

To evaluate the participation of nitric oxide (NO) on pressure-induced natriuresis in pentobarbital-anesthetized dogs, renal perfusion pressure (RPP) was increased twice from 100 to 150 mmHg before and during the intrarenal administration of an NO-synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), while determining changes in glomerular filtration rate (GFR), renal blood flow (RBF), and urine sodium and water excretion. Before the inhibition of NO, the increase in RPP induced diuresis (5-fold) and natriuresis (4.2-fold) with no change in RBF or GFR. However, the intrarenal infusion of L-NAME (1 microgram.kg-1.min-1) blunted the diuretic and natriuretic responses without altering RBF or GFR. The infusion of the NO synthesis precursor L-arginine prevented the inhibitory effect that L-NAME exerted on the diuretic and natriuretic responses to the increase in RPP. These results indicate that the increase in RPP stimulates NO synthesis and suggest that NO might play an important role in the control of sodium and water excretion during acute changes in RPP.

Animals↗
PubMed1992

Role of the endothelium-dependent relaxing factor nitric oxide on renal function.

The role of nitric oxide in renal function has been assessed with pharmacologic and physiologic interventions. Pharmacologically, the renal vasodilation and, to some extent, the natriuresis produced by endothelium-dependent vasodilators such as acetylcholine and bradykinin are mediated by nitric oxide and also by prostaglandins. However, prostaglandins and nitric oxide do not participate in the renal effects produced by endothelium-independent vasodilators such as atrial natriuretic peptide, prostaglandin I2, and nitroprusside. Physiologically, nitric oxide and prostaglandins exert a strong regulation on the effects produced by changes in renal perfusion pressure. Increments in renal perfusion pressure within the range of RBF autoregulation appear to inhibit prostaglandin synthesis while simultaneously enhancing the formation of nitric oxide. Nitric oxide modulates autoregulatory vasoconstriction and at the same time inhibits renin release. Conversely, a decrease of renal perfusion pressure to the limit of or below RBF autoregulation may inhibit the synthesis of nitric oxide but may trigger the release of prostaglandins, whose vasodilator action ameliorates the fall in RBF and stimulates renin release. Nitric oxide and prostaglandins are also largely responsible for mediating pressure-induced natriuresis. However, unlike prostaglandins, mild impairment of the synthesis of nitric oxide in systemic circulation produces a sustained decrease in sodium excretion, which renders blood pressure susceptible to be increased during high-sodium intake. This effect suggests that a deficiency in the synthesis of nitric oxide could constitute the most effective single disturbance to foster the development of a syndrome similar to that seen in salt-sensitive hypertension.

Animals↗
PubMed1992

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)

Adult↗
PubMed1992

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.

Blood Pressure↗
PubMed1992

Deficient production of nitric oxide induces volume-dependent hypertension.

AIM: To study the influence of nitric oxide on renal function. DESIGN: Nitric oxide synthesis was inhibited and the effects on renal parameters were determined. METHODS: Nitric oxide synthesis was progressively blocked by the intravenous administration of increasing doses of NG-nitro-arginine methylester (L-NAME) and then (c)GMP was administered. RESULTS: The blockade of nitric oxide synthesis first induced a marked fall in urinary sodium excretion, and later, a sustained increase in mean arterial pressure. These effects were reversed by 8-bromide cGMP. Nitric oxide-dependent cGMP formation was higher in the inner medulla than in any other part of the renal parenchyma, and the inhibition of nitric oxide synthesis significantly decreased both pressure- and volume expansion-induced natriuresis. CONCLUSIONS: Both the natriuretic and vasodilator tone maintained by nitric oxide are ultimately due to the production of cGMP. Nitric oxide-induced formation of cGMP appears to be the major factor that links changes in renal medullary circulation to those of sodium excretion. Sufficient inhibition of nitric oxide synthesis to decrease sodium excretion without altering blood pressure induces volume-dependent hypertension because blood pressure is elevated by an increased sodium intake.

Animals↗
PubMed1991

Mediatory role of endothelium-derived nitric oxide in renal vasodilatory and excretory effects of bradykinin.

Intrarenal infusions of 5 ng/kg/min bradykinin (BK) in 5 mg/kg intravenous bolus meclofenamate-treated anesthetized dogs significantly increased renal blood flow, diuresis, natriuresis, and kaliuresis. All these effects were abolished by the simultaneous intrarenal infusion of a competitive inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (LNMMA). Furthermore, the intrarenal infusion of this inhibitor alone also produced a significant decrease in basal renal blood flow. The administration of L-arginine, a precursor of nitric oxide, prevented the inhibitory effect of LNMMA on the renal vasodilatory and excretory response to BK. Glomerular filtration rate and mean arterial pressure did not change throughout the experiment. It is concluded that the renal vasodilatory and excretory responses to intrarenal BK in meclofenamate-treated dogs are largely dependent on endothelium-derived nitric oxide.

Animals↗
PubMed1991

A single mechanism to explain the effect of calcium on renal function.

It is known that calcium induces the formation of potent vasodilators in endothelial cells and vasoconstriction in smooth muscle cells, whereas in the renal parenchyma, it modulates sodium excretion through vascular and tubular mechanisms. Consequently, an increased concentration of calcium in renal circulation may induce a sequence of contrasting hemodynamics and excretory effects depending on the threshold of a particular mechanism that is first being stimulated. In order to identify this sequence of responses and their respective thresholds, we infused into the renal artery of anesthetized dogs progressively increasing doses of calcium gluconate that ranged from 1 to 400 micrograms/kg/min. The administration of 1, 10, and 100 micrograms/kg/min of calcium gluconate was followed by a significant increase in urinary excretion of PGE2 and 6-keto-PGF1 alpha and by a marked diuresis and natriuresis without altering renal blood flow (RBF) or glomerular filtration rate (GFR). Renin release was increased by 80% only during the infusion of the 10 micrograms/kg/min dose. The intrarenal infusion of a 400 micrograms/kg/min dose of calcium produced marked decreases in RBF and GFR, while urine sodium excretion (UNaV), UPGE2V, and U6-keto-PGF1 alpha V continued and were markedly elevated. During all these maneuvers, mean arterial pressure remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗