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V Lahera

Publications and source records attributed to V Lahera.

68 records · Page 4Linked to original sources
PubMed1991

Role of prostaglandins and endothelium-derived relaxing factor on the renal response to acetylcholine.

Acetylcholine (ACh) stimulates the endothelial release of prostacyclin and endothelium-derived relaxing factor (EDRF). However, the relative participation of these substances in mediating the renal effects of ACh remains undefined. To elucidate this issue, we studied the modifications of renal responses to intra-renal ACh infusion (25 ng.kg-1.min-1) produced by blocking the synthesis of EDRF and/or prostaglandins (PG) in anesthetized dogs. ACh induced a significant increase in renal blood flow (RBF) (34%), urine volume (UV) (450%), and urinary sodium excretion (UNaV)(259%), which remained unaltered after blocking the synthesis of EDRF [NG-monomethyl-L-arginine (LNMMA), 50 micrograms.kg-1.min-1 intrarenal] or PG (meclofenamate, 5 mg/kg iv). However, the simultaneous administration of meclofenamate and LNMMA prevented the ACh-induced increase in RBF and UV but not in UNaV. The concomitant infusion of L-arginine but not D-arginine prevented these blocking effects of LNMMA. It was concluded that the ACh-induced increases in RBF and UV, but not UNaV, are mediated by both PG and EDRF. The hemodynamic and diuretic effect of either one of these mediators can be fully compensated during the blockade of the other.

Acetylcholine↗
PubMed1991

Effects of NG-nitro-L-arginine methyl ester on renal function and blood pressure.

The dose-dependent effects of intravenous infusions of nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 1, 10, and 50 micrograms.kg-1.min-1), were studied in anesthetized rats to determine whether the inhibitory actions of L-NAME are manifested primarily in alterations of renal function or whether they are the consequences of the increase in systemic blood pressure. Mean arterial pressure (MAP) was not altered by the intravenous L-NAME infusions of 0.1 and 1.0 microgram.kg-1.min-1. However, 0.1 microgram.kg-1.min-1 L-NAME induced a 30% decrease in urine flow rate (UV). The administration of 1.0 microgram.kg-1.min-1 L-NAME, in addition to decreasing UV, also decreased urinary sodium excretion (UNaV) and renal plasma flow (RPF). The intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 produced significant increases in MAP that reversed the initial fall in UV and UNaV, despite decreasing RPF and glomerular filtration rate (GFR). The administration of L-arginine alone (10 micrograms.kg-1.min-1) did not modify any of the parameters measured, but it effectively prevented all the hemodynamic and renal changes induced by the infusion of 50 micrograms.kg-1.min-1 L-NAME. These results suggest that the decrease in nitric oxide production induced by the intravenous infusion of L-NAME affects renal excretion of sodium and water in the absence of any significant change in blood pressure. At larger doses, L-NAME also produces hypertension that overrides the initial antinatriuretic effect.

Animals↗
PubMed1990

Role of prostaglandins in the renal response to calcium infusion.

The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca.kg-1.min-1) on renal hemodynamics and on renal excretory function were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 min each (1 ml/min). In a second group, the same doses were administered 30 min after the start of an infusion of prostaglandin (PG) inhibitors (intrarenal indomethacin, 10 micrograms.kg-1.min-1, or intravenous bolus injection of meclofenamate, 5 mg/kg). No change with physiological significance was observed during the infusion of 10 micrograms Ca.kg-1.min-1. However, the infusion of 100 micrograms Ca.kg-1.min-1 induced increases (P less than 0.05) in glomerular filtration rate (50%), sodium excretion rate (180%), and fractional excretion of sodium (160%), with respect to control precalcium values. All these changes were prevented by the concurrent administration of PG synthesis inhibitors. Urinary PGE2 and 6-keto-PGF1 alpha increased 220 and 85%, respectively, during the infusion of 100 micrograms Ca.kg-1.min-1, but both decreased (P less than 0.05) below basal levels during the concurrent administration of PG synthesis inhibitors. The infusion of 100 micrograms Ca.kg-1.min-1 decreased (P less than 0.05) renal blood flow by 16% during the administration of PG synthesis inhibitors. These results suggest that PGs are mediating the increase in hemodynamic and excretory factors induced by the intrarenal infusion of 100 micrograms Ca.kg-1.min-1.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Stimulation of renin release by intrarenal calcium infusion.

The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca/kg/min) on renin secretion were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 minutes each (1 ml/min). In a second group, the same doses were administered 30 minutes after the start of infusion of prostaglandin synthesis inhibitors (indomethacin 10 micrograms/kg/min intrarenal or injection of meclofenamate 5 mg/kg i.v. bolus). Mean arterial pressure, renal blood flow, and glomerular filtration rate remained unchanged during the infusion of calcium in both groups. The infusion of 10 micrograms Ca/kg/min increased renin secretion 77% and sodium excretion 123%. During the infusion of 100 micrograms Ca/kg/min, renin secretion was not different from precalcium values, whereas urinary 6-keto-PGF1 alpha, urine flow, sodium, potassium, and calcium excretion rates were increased (p less than 0.05). During the administration of prostaglandin synthesis inhibitors, the urinary 6-keto-PGF1 alpha levels were reduced, and the infusion of 10 micrograms Ca/kg/min failed to increase renin secretion, sodium excretion, or 6-keto-PGF1 alpha excretion rates. The infusion of 100 micrograms Ca/kg/min during prostaglandin synthesis inhibition did not modify urine flow or sodium excretion; however, potassium and calcium excretions increased. It is concluded that 1) the intrarenal infusion of small doses of calcium gluconate is capable of stimulating renin secretion through a prostaglandin-mediated mechanism, and 2) the stimulation of renin secretion as well as the increase in sodium excretion induced by calcium are independent of hemodynamic alterations.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Effects of NG-monomethyl-L-arginine and L-arginine on acetylcholine renal response.

Intrarenal infusion of acetylcholine in meclofenamate-treated dogs significantly increased renal blood flow, diuresis, and natriuresis. Intrarenal infusions of either NG-monomethyl-L-arginine (inhibitor of endothelium-derived relaxing factor formation), or L-arginine (precursor of endothelium-derived relaxing factor formation) did not modify basal levels of those parameters. However, the infusion of NG-monomethyl-L-arginine inhibited the acetylcholine-induced increases in renal blood flow and diuresis without affecting natriuresis, which increased significantly. The infusion of L-arginine failed to further enhance hemodynamic and excretory effects elicited by acetylcholine. The concomitant infusion of L-arginine and NG-monomethyl-L-arginine did not change renal blood flow, urine flow, or sodium excretion rate. L-Arginine administration prevented the inhibitory effect of NG-monomethyl-L-arginine on acetylcholine-induced renal vasodilatation and diuresis. Glomerular filtration rate and mean arterial pressure did not change throughout the experiment. The results indicate that the vasodilatory and diuretic responses to intrarenal acetylcholine in meclofenamate-treated dogs are largely dependent on endothelium-derived relaxing factor.

Acetylcholine↗
PubMed1989

Role of renal prostaglandins in the action of ramipril (HOE-498) in normotensive rats.

Changes in blood pressure, plasma renin activity, urine volume, urinary PGE2, 6-keto-PGF1 alpha and kinins, were studied after the administration of the angiotensin converting enzyme inhibitor ramipril (100 mu/kg/day), for one week in concomitantly indomethacin (1 mg/kg/day) treated and untreated rats. Measurements were made basally, before Ramipril administration and on days 1 and 7 during the treatment. Ramipril given alone induced a decrease in urinary PGE2 (NS) and 6-keto-PGF1 alpha (p less than 0.05) on day 1, together with an increase in urinary kinins on day 7 (p less than 0.01) and in urine volume on days 1 and 7 (p less than 0.05). Increased urinary PGE2 (NS) and 6-keto-PGF1 alpha (p less than 0.05) were observed in indomethacin pretreated rats after ramipril administration. No modifications in BP levels were observed either with indomethacin or with ramipril given alone or with ramipril plus indomethacin. Ramipril increased plasma renin activity levels both in indomethacin treated and untreated rats on days 1 (p less than 0.01) and 7 (p less than 0.05). The diuretic effect of ramipril and the stimulation of kinins were blunted when concomitant indomethacin was administered. Although a stimulatory effect of ramipril on urinary PGS was only observed during indomethacin administration, the present results would suggest that a non-inhibited PGS synthesis would be required for the renal actions of Ramipril.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Characterization of the renal effects of an intravenous calcium gluconate infusion in normotensive volunteers.

The effects on renal function of an intravenous infusion of calcium gluconate at subpressor doses have been investigated in a group of seven normotensive male volunteers. In the absence of changes in blood pressure, the calcium gluconate induced a significant increase in renal plasma flow and the glomerular filtration rate (P less than 0.01) with a significant fall in the filtration fraction (P less than 0.01). Both diuresis and natriuresis increased significantly (P less than 0.01), plasma renin activity fell (P less than 0.01) and the urinary excretion of 6-keto prostaglandin F1 alpha (PGF1 alpha) and prostaglandin E2 (PGE2) increased (P less than 0.01). These results indicate that calcium infusion at subpressor doses has renal vasodilating, diuretic and natriuretic properties that appear to be facilitated by an increase in the renal production of vasodilatory and natriuretic prostaglandins.

Adult↗
PubMed1988

Comparison of the effects of calcium antagonists and converting enzyme inhibitors on renal function under normal and hypertensive conditions.

Calcium antagonists decrease the ability of the kidney to autoregulate renal blood flow (RBF) and glomerular filtration rate (GFR). Therefore, when afferent renovascular resistance is elevated, as in essential hypertension, there is a resultant increase in RBF and GFR with the administration of calcium antagonists. These agents also induce a marked natriuresis because of direct tubular action through unknown mechanisms. The natriuresis can be dissociated from renal and systemic hemodynamic actions, indicating that the decreased sodium reabsorption could override other compensatory mechanisms explaining the absence of sodium retention during the treatment. The renal effects of converting enzyme inhibitors (CEIs) can be explained by the reduction of intrarenal formation in angiotensin II. Because the activation of the renin-angiotensin system is mainly responsible for inducing sodium retention during a decrease in systemic blood pressure, CEIs could have a protecting effect without disturbing other homeostatic mechanisms. CEIs decrease efferent glomerular resistance, reducing capillary pressure and thereby reducing GFR. This effect is not translated in sodium retention because the reduction of GFR is mild during captopril administration in kidneys with normal or increased renal perfusion pressure. At low renal perfusion pressure, the reduced glomerular afferent vasoconstriction can compromise GFR, leading to renal insufficiency. Although these situations are not likely to be encountered during the treatment of uncomplicated essential hypertension, in severe hypertension with hypertrophy of pre-glomerular vessels, glomerular perfusion may decrease. Combination therapy of calcium antagonists and CEIs has been reported to be an effective treatment of severe hypertension. Currently, little information is available on the manner in which renal function is affected by simultaneous administration of both drugs.

Angiotensin II↗
PubMed1988

Acute effect of potassium canrenoate administration on renin-angiotensin, kallikrein-kinin and prostaglandin systems.

1. To investigate the possible effects of potassium canrenoate (PC) on plasma renin activity (PRA) and on renal prostaglandins (PGS) and kinins under elevated sodium and/or potassium intakes, a single dose of PC was administered to four groups of Wistar male rats. 2. They were fed a normal diet (C), a diet supplemented with 4% of NaCl, (Na), with 1% of KCl: (K) or both supplements (NaK). 3. PRA and urinary PGS excretion did not show changes after PC administration, but total urinary kinins showed higher values after the treatment in all groups. 4. A diuretic but not natriuretic effect was observed only in C animals. 5. In conclusion, the single dose of PC was able to stimulate urinary kinins and to spare potassium independently of dietary electrolyte supplements that were able to block the diuretic effect of the drug.

Animals↗
PubMed1986

Effect of ZK 36 374 on blood pressure, diuresis, plasma renin activity and urinary excretion of prostaglandin E2 and sodium.

ZK 36 374 is a chemically stable prostacyclin analogue which has been demonstrated to be a potent vasodilator. The effects of the drug on blood pressure, plasma renin activity, diuresis and urinary excretion of prostaglandin E2 and sodium, were studied on the 1st and 7th days of treatment and a week after the end of the administration to rats submitted to the following experimental situations: Goldblatt 2k-1c, Goldblatt 2k-1c + 5% NaCl loading, 5% NaCl loading, and controls. ZK 36 374 was continuously administered during one week by an osmotic pump subcutaneously implanted and connected to the right jugular vein. Twenty four hours after the pump implantation, blood pressure decreased in the three experimental groups. At the 7th day, pressure remained at similar levels except in NaCl loaded rats where an increase was observed. At the 15th day pressure levels returned to pretreatment values. On the 7th day of treatment urinary PGE2 showed higher values than pretreatment ones, to return to pretreatment at the 15 day. Sodium excretion showed an increase on the 7th day and was even higher on the 15th day. Plasma renin activity levels remained unchanged during the treatment except in the Goldblatt 2k-1c group which showed a significant fall at the 7th day. All the changes described on the 1st day of treatment might be related to counteraction of the blood pressure decrease on the same day.

Animals↗
PubMed1986

Different excretion pattern of urinary PGE2 and 6-keto-PGF1 alpha in two kidney-one clip Goldblatt rats.

Changes in blood pressure and 24 hour urinary excretion of PGE2 and 6-keto-PGF1 alpha have been studied during ten weeks after renal artery clipping or sham operation in rats. From the second week on, systolic blood pressure was significantly increased in the two kidney-one clip rats as compared to controls. Maximal differences were reached in the 10th week after the operation (145 +/- 8 vs 116 +/- 3.2 mm Hg; p less than 0.001). Urinary PGE2 levels showed markedly elevated values versus controls from the 6th week on (p less than 0.001). However, no significant changes in urinary 6-keto-PGF1 alpha excretion were observed between the groups during the whole experimental period. These findings suggest that renal PGE2 may be involved in the pathophysiology of blood pressure control in the two kidney-one clip model, whereas, 6-keto-PGF1 alpha seems not to be altered after renal artery clipping.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Simple radioimmunological method for urinary 6-keto-PGF1 alpha measurement.

A radioimmunoassay for the determination of 6-keto-PGF1 alpha (stable metabolite of Prostacyclin) in urine using a specific antiserum, is described. The antibody used, showed no significant cross-reactivity with other PGS. (3H)-6-keto-PGF1 alpha has been used as tracer and a 30% Hydroxyapatite suspension was utilized for the separation of bound and free fractions. Standard curve ranges between 2 and 1000 pg thus allowing measurements in urine. Aliquots of 0.2 to 1 ml of 24 hours urinary samples were submitted to a preextraction step with Hexane in order to eliminate neutral fats. After acidifying with 0.1 N HCl to pH = 3.5-4, an Ethyl Ether extraction step was performed showing a recovery of 66%. Repeated analysis of a rat urine pool, showed 7.7 intraassay and 9.8 interassay variation coefficients. Values obtained amounted to 38.3 +/- 4.6 ng/24 h in normal rats and 133 +/- 32 ng/24 h in 5% NaCl loaded rats (p less than 0.001). The values obtained in healthy men were 508 +/- 94 ng/24 h and in women 375 +/- 136 (p less than 0.05).

6-Ketoprostaglandin F1 alpha↗
PubMed1984

A radioimmunoassay method for measurement of urinary kinins.

A sensitive and specific radioimmunoassay for measuring urinary kinins was developed. Antibodies against bradykinin were induced in rabbits by injecting bradykinin coupled to bovine albumin. One of the antisera generated was used at a final dilution of 1:18,000 to obtain a 30% total binding of bradykinin-(8-tyrosine)-[125I]-triacetate. Synthetic bradykinin (5-1,000 pg) was used as standard in the curves. The sensitivity of the assay was 5 pg. The recovery of bradykinin added to urinary samples was 86.85 +/- 6%. The intraassay and interassay coefficients of variation were 3.3% (n = 12) and 4.4% (n = 5), respectively. The antiserum showed no cross-reactivity with oxytocin or low molecular weight kininogen and cross-reacted with kallidin (lys-bradykinin), met-kallidin, and angiotensin I, but cross-reaction with angiotensin I (2.5%) was low enough to be disregarded. The mean urinary levels of total kinins in 12 normal subjects were 23.2 +/- (SEM) 2.2 micrograms/day.

Adult↗