Influence of renal nerves and sodium balance on the acute antidiuretic effect of bendroflumethiazide in rats with diabetes insipidus.

To examine the role of the renal nerves and sodium depletion for the acute antidiuretic response to bendroflumethiazide (BFTZ; 25 microg/hr) in rats with diabetes insipidus (DI), renal clearance experiments were performed in the following groups of conscious, chronically instrumented male Brattleboro rats with vasopressin-deficient DI: Control (n = 7), BFTZ (n = 9), BFTZ + sodium replacement (n = 7) and BFTZ + chronic bilateral renal denervation (n = 6). Urine flow rate and urinary sodium concentration were measured drop-by-drop with a sodium-sensitive electrode and by collection of urine in vials placed on an electronic balance. This allowed computer driven, servo-controlled, independent i.v. replacement of sodium and fluid losses, respectively. Mean arterial pressure, glomerular filtration rate (GFR) and proximal tubular water and sodium handling, assessed by lithium clearance (C(Li)), were stable in the control group. BFTZ produced a marked antidiuretic response (deltaV = -79%; deltaUrine osmolality = +218%) associated with decreases in GFR (-28%), C(Li) (-62%), free water clearance (-100%) and plasma Na (-5 mM). Fractional water reabsorption was increased by 19% in the proximal tubules and by 7% in segments beyond. Sodium replacement did not modify the fall in GFR or the antidiuresis, but partly prevented the increase in fractional proximal water reabsorption. Bilateral renal denervation did not affect the response to BFTZ. We conclude that the acute antidiuretic effect of BFTZ is independent of sodium balance and renal nerve activity and is elicited by a reduction in GFR accompanied by an increase in fractional water reabsorption in the proximal tubules and in the distal nephron.

Renal function after myocardial infarction and cardiac arrest in rats: role of ANP-induced albuminuria?

Renal function was measured by clearance technique before and after acute myocardial infarction (MI) induced by left coronary artery ligation in male Sprague-Dawley rats. The animals were anaesthetized with halothane-nitrous oxide, paralysed with pancuronium and artificially ventilated. All parameters were stable throughout the experiment in sham-operated time control animals (n = 8). After MI, rats developed left ventricular dysfunction with increased left ventricular end-diastolic pressure and decreased mean arterial pressure. MI produced antidiuresis and antinatriuresis without changes in glomerular filtration rate (GFR), lithium clearance or renal albumin excretion (n = 8). The antidiuretic and antinatriuretic responses to MI were similar in rats with chronic bilateral renal denervation (n = 5). Three additional rats with chronic bilateral renal denervation had cardiac arrest and were resuscitated with cardiac massage, i.v. lidocaine and intracardiac adrenaline administration. These animals showed a transient increase in urine flow rate, sodium and albumin excretion with maximum 30-60 min after resuscitation, while GFR and lithium clearance were normal. Since cardiac ischaemia and sympathetic stimulation are strong stimuli for the release of atrial natriuretic peptide (ANP), we examined if ANP (0.25, 0.50, and 1.00 microg kg(-1) min(-1), n = 8 per dose) affects urinary albumin excretion. ANP increased dose-dependently the urine/plasma concentration ratio of albumin relative to inulin, which suggests that ANP increases the glomerular permeability for albumin. We conclude that MI causes stimulation of renal tubular sodium and water reabsorption by a mechanism which is independent of intact renal innervation. MI does not produce any change in renal albumin excretion in rats, but transient albuminuria may be observed in rats following cardiac arrest and/or manoeuvres used in cardiac resuscitation. Since ANP produces albuminuria, we speculate that ANP may be an important mediator of albuminuria in states with elevated plasma concentrations of ANP.

Antihypertensive action of non-natriuretic doses of furosemide in Dahl salt-sensitive rats.

BACKGROUND: That non-natriuretic doses of loop diuretics exert an antihypertensive action has been suggested, but not confirmed, by simultaneous measurements of the arterial pressure and sodium balance during therapy. OBJECTIVE: To examine the relationship between changes in arterial pressure and changes in sodium balance during furosemide treatment. DESIGN: Twenty hypertensive Dahl salt-sensitive rats fed a 4% NaCl diet were allocated to four groups and administered the following treatments: placebo once a day intraperitoneally, continuous infusion of 4 mg/day furosemide intraperitoneally, 4 mg furosemide once a day intraperitoneally and 12 mg furosemide once every third day intraperitoneally. METHODS: The mean arterial pressure (MAP) was measured continuously with radiotelemetry and the sodium balance was measured with the rats in metabolic cages. RESULTS: Administration of furosemide as a bolus injection once a day (P < 0.01) or once every third day (P < 0.05) lowered the MAP significantly compared with placebo, whereas continuous infusion of furosemide had no significant effect on the MAP (P < 0.07). Fast Fourier transformation analysis detected an acute antihypertensive action related to the temporary diuretic and natriuretic responses during the period 0-6 h after intraperitoneal bolus injections of 4 and 12 mg furosemide. None of the treatment regimens produced 24 h sodium or potassium losses. At the end of the study, the total body water, extracellular fluid volume, total body sodium and potassium were similar for rats in all groups. CONCLUSIONS: Furosemide has an acute antihypertensive action in Dahl salt-sensitive rats fed a 4% NaCl diet that is related to renal sodium and volume losses whereas the long-term antihypertensive effect is independent of changes in extracellular fluid volume, total body water, sodium and potassium.

Effects of renal papillary-medullary lesion on the antihypertensive effect of furosemide and development of salt-sensitive hypertension in Dahl-S rats.

To test the hypothesis that the long-term antihypertensive action of furosemide is mediated by a renomedullary vasodepressor substance, we measured mean arterial pressure (MAP) by radiotelemetry in Dahl-S rats with either intact or bromoethylamine-induced (BEA, 100 mg/kg i.p.) lesion of the renal papilla and medulla. Seven days of recovery after BEA administration, the rats diet was changed from 1 to 4% NaCl, and during days 8 to 31, rats were randomized to daily treatment with placebo or furosemide (50 mg/kg p.o.). Then furosemide treatment was stopped and the rat food was changed to 1% NaCl diet. After a 10-day wash-out period, renal function was measured. BEA produced a rapid (within min) and sustained increase in MAP which was accelerated during 4% NaCl diet. Furosemide prevented 4% NaCl-induced hypertension in both rats with intact kidneys and in rats with BEA-induced renal papillary-medullary lesion. A significant decrease in renal plasma flow (-34%) and glomerular filtration rate (-40%) was observed in all BEA-treated rats independent of previous furosemide treatment. In response to an i.v. load of isotonic saline (10% body weight), rats with renal papillary-medullary lesion had an impaired ability to excrete sodium. Histological examination showed that BEA-treated rats had severe lesions of the renal papilla and medulla, with light-to-moderate changes in the renal cortex. It is concluded that the antihypertensive effect of furosemide is not mediated by a renomedullary vasodepressor substance. The accelerated NaCI-sensitive hypertension in rats with BEA-induced renal papillary-medullary lesion is related to an impaired ability to excrete excess NaCl.