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Pulmonary vasodilator responses to nitroprusside and nitroglycerin in the dog.

The objective of this study was to determine the direct actions of nitroprusside and nitroglycerin on the pulmonary vascular bed in the intactchest dog. These widely used nitrogen oxide-containing vasodilator agents decreased pulmonary arterial pressure and increased cardiac output without altering left atrial pressure. Reductions in pulmonary arterial pressure and pulmonary vascular resistance were small under resting conditions, but were enhanced when pulmonary vascular tone was elevated by infusion of a stable prostaglandin analog that increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In studies in which pulmonary blood flow to the left lower lobe was maintained constant, nitroprusside and nitroglycerin caused small but significant reductions in lobar arterial and small-vein pressures without significantly affecting left atrial pressure. With constant blood flow, lobar vascular pressures that were reduced in response to the vasodilators were more greatly reduced when lobar vascular resistance was increased by infusion of the prostaglandin analog or serotonin. However, when lobar vascular pressures were elevated by passive obstruction of lobar venous outflow, vasodilator responses to nitroprusside and nitroglycerin were not enhanced. These data suggest that nitroprusside and nitroglycerin decrease pulmonary vascular resistance by dilating intrapulmonary veins and upstream segments. These responses were minimal under control conditions but were enhanced when vascular tone was increased. This vasodilator action is independent of passive factors such as changes in pulmonary blood flow or left atrial pressure and is not secondary to an effect of these agents on the systemic circulation. Pulmonary vasodilator responses to nitroprusside and nitroglycerin were, however, found to be dependent on the existing level of vasomotor tone in the pulmonary vascular bed.

Animals↗

Nicardipine versus nitroprusside infusion as antihypertensive therapy in hypertensive emergencies.

This prospective study compared the efficacy of nicardipine and nitroprusside for treating hypertensive emergencies by measuring haemodynamic indices and serum catecholamine levels. Patients admitted to the emergency department with a hypertensive crisis and acute pulmonary oedema received intravenous infusions of nitroprusside (starting dose 1 microgram/kg per min, n = 20) or nicardipine (starting dose 3 micrograms/kg per min, n = 20). Both groups experienced significant declines in systolic and diastolic blood pressure after treatment, but there were no significant time-dependent differences between the groups. Heart rate decreased in the nicardipine group and increased in the nitroprusside group, but neither change was significant. Respiration rate decreased and capillary oxygen saturation rate increased after treatment in both groups. Adrenaline and noradrenaline levels decreased significantly after treatment in both groups; noradrenaline levels were significantly decreased in the nicardipine-treated group compared with the nitroprusside-treated group. Injectable nicardipine is easy to use and as effective as nitroprusside for treating hypertensive crisis with acute pulmonary oedema.

Aged↗

Cardiovascular function during induced hypotension by fenoldopam or sodium nitroprusside in anesthetized dogs.

Fenoldopam, a selective dopamine1 receptor agonist, has been recommended for induced hypotension because it effectively lowers arterial blood pressure and improves renal perfusion. We examined cardiovascular functions during hypotension induced by fenoldopam or sodium nitroprusside. In eight halothane-anesthetized dogs, the left ventricle (LV) was instrumented with pressure and ultrasonic dimension transducers for the assessment of LV contractility using the analysis of the pressure-diameter relationship. Blood flow distribution was measured by radioactive microspheres. Doses of fenoldopam and nitroprusside were titrated to reduce mean arterial blood pressure to 60 mm Hg. After 40 min of hypotension, fenoldopam and nitroprusside caused similar increases in heart rate (17% +/- 4% vs 19% +/- 10%, respectively) and decreases in systemic vascular resistance (-24% +/- 5% vs -27% +/- 4%). Hypotension induced by fenoldopam was associated with higher LV end-diastolic pressure (4.4 +/- 0.6 vs 2.5 +/- 1.1 mm Hg) and end-systolic meridional wall stress (33.0 +/- 4.3 vs 17.8 +/- 2.1 g/cm2) when compared with nitroprusside. There were no significant changes in cardiac output and cardiac contractility as expressed by the slope (Ees) of the LV end-systolic pressure-diameter relationship, velocity of shortening of the diameter, and percentage of wall thickening of the LV. In contrast to nitroprusside, which decreased renal blood flow from 197 +/- 19 to 163 +/- 15 mL/min, renal blood flow increased during fenoldopam-induced hypotension from 187 +/- 20 to 239 +/- 18 mL/min. The increase in renal perfusion was similar in upper, middle, and lower regions of the kidney; however, it was more in the medulla compared with the cortex (37% +/- 17% vs 25% +/- 7%).(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Comparison of the effects of nitric oxide, nitroprusside, and nifedipine on hemodynamics and right ventricular contractility in patients with chronic pulmonary hypertension.

STUDY OBJECTIVES: The effects of inhaled nitric oxide (NO) on hemodynamics and right ventricular (RV) contractility were compared with those of nitroprusside and nifedipine in 14 patients with severe chronic pulmonary hypertension. STUDY DESIGN: Micromanometer and balloon-tipped right heart catheterization were performed. Inhaled NO, IV nitroprusside, and sublingual nifedipine were administered sequentially while patients breathed > 90% oxygen. SETTING: Cardiac catheterization laboratory in a tertiary care teaching hospital. PATIENTS: Fourteen patients with severe pulmonary hypertension unrelated to left ventricular dysfunction. MEASUREMENTS AND RESULTS: During NO inhalation, mean systemic arterial pressure (MAP) was unchanged, but pulmonary artery (PA) pressure ([mean +/- SEM] 49 +/- 2 mm Hg vs 44 +/- 2 mm Hg; p < 0.01), pulmonary vascular resistance (PVR; 829 +/- 68 vs 669 +/- 64 dyne x s x cm(-5); p < 0.01) and RV end-diastolic pressure (RVEDP; 12 +/- 1 vs 10 +/- 1 mm Hg; p < 0.01) decreased. Stroke volume index (SVI; 31 +/- 2 vs 35 +/- 3 mL/m(2); p < 0.05) increased, and the first derivative of RV pressure at 15 mm Hg developed pressure (RV +dP/dt at DP15) was unchanged. During nitroprusside administration, MAP decreased (105 +/- 5 vs 76 +/- 5 mm Hg; p < 0.01), PA was unchanged (48 +/- 2 vs 45 +/- 3 mm Hg; p = not significant), and PVR decreased (791 +/- 53 vs 665 +/- 53 dyne x s x cm(-5); p < 0.01). RV +dP/dt at DP15 increased (425 +/- 22 vs 465 +/- 29 mm Hg/s; p < 0.05), but SVI was unchanged. Nifedipine decreased MAP (103 +/- 5 vs 94 +/- 5 mm Hg; p < 0.01), PA and PVR were unchanged, RVEDP increased (12 +/- 1 vs 14 +/- 2 mm Hg; p < 0.01), and RV +dP/dt at DP15 decreased (432 +/- 90 vs 389 +/- 21 mm Hg/s; p < 0.05). CONCLUSIONS: Inhaled NO is a selective pulmonary vasodilator in patients with chronic pulmonary hypertension that improves cardiac performance without altering RV contractility. Nitroprusside caused a similar degree of pulmonary vasodilation. In contrast to inhaled NO, nitroprusside caused systemic hypotension associated with an increase in RV contractility. Acute administration of nifedipine did not cause pulmonary vasodilation, but RVEDP increased and RV contractility decreased.

Administration, Inhalation↗

Regional coronary flow and contraction after partial coronary obstruction. Comparative effects of nitroglycerin and nitroprusside.

Following partial coronary occlusion, the comparative effects of administration of nitroglycerin and nitroprusside on aortic perfusion pressure, coronary flow, local tendon, and segmental length were assessed. Partial coronary occlusion decreased coronary flow from 78.9 +/- 5.0 ml/gm to 40.6 +/- 2.6 ml/100 gm and total tension to 76.9 +/- 5.6 percent of the control value. Nitroglycerin and nitroprusside improved total tension to a similar degree with a reduction of either 10 or 20 mm Hg in systolic pressure; however, when systolic pressure was reduced by 30 mm Hg, nitroglycerin decreased total tension slightly but insignificantly, while nitroprusside significantly decreased ischemic zone tension. Changes in segment length shortening paralleled changes in total tension. Thus, in the presence of partial coronary occlusion, both nitroglycerin and nitroprusside similarly affect coronary blood flow, total tension, and systolic shortening at a decrease of 10 and 20 mm Hg in systolic pressure; however, at a decrease of 30 mm Hg, both nitroglycerin and nitroprusside decrease total tension and systolic shortening.

Animals↗

Analysis of cardiac actions of nitroprusside in intact dogs and in isolated atria.

The effects of intravenous administration of sodium nitroprusside to a donor dog on cardiac pacemaker activity and contractility were investigated in a cross-circulated dog heart preparation; i.e., the isolated atrial muscle was perfused with blood from a pentobarbital anesthetized donor dog. Intravenous administration of nitroprusside (1-10 micrograms/Kg) caused a hypotension with tachycardia, and occasionally with bradycardia. This effect was blocked by atropine injections into the donor dog, but no significant chronotropic and inotropic changes were observed in the isolated atria. Larger doses (over 100 micrograms/Kg) of nitroprusside produced positive chronotropic and inotropic effects in isolated atria, which were inhibited completely by propranolol. Moreover, direct intraarterial injection of nitroprusside (10-1,000 micrograms) had no significant chronotropic and inotropic effects in isolated atria, although acetylcholine (0.01-0.1 micrograms) induced negative chronotropic and inotropic effects. From these results, it is concluded that nitroprusside has no direct cardiac effect and that it causes a release of catecholamines in doses which produce a profound hypotension.

Acetylcholine↗

Stimulating and potentiating effects of sodium nitroprusside on the guinea-pig vas deferens and their comparison with the effects on the portal vein and the taenia coli.

The effects of sodium nitroprusside on the electrical and mechanical properties of the guinea-pig vas deferens were studied and compared with those on the portal vein and the taenia coli. Sodium nitroprusside at concentrations higher than 0.5 mM caused depolarization of the membrane of the vas deferens and initiated spontaneous contractions, while spontaneous contractions of the portal vein were blocked by similar concentration of the drug. Noradrenaline- and carbachol-induced contractions of the vas deferens were markedly potentiated by sodium nitroprusside, whereas the noradrenaline-induced contraction of the portal vein was suppressed by the same concentration of the drug. Increasing the K+ concentration by 15 to 30 mM caused a similar potentiation of the contraction by noradrenaline or carbachol in the vas deferens. When sodium nitroprusside was applied during the course of noradrenaline- or carbachol-induced contracture, contraction was observed in the vas deferens, while relaxation was induced in the portal vein and taenia coli. In either case, however, the addition of Ca caused a relaxation of the preparations. These results suggest that the membrane depolarization may be involved in the stimulating effects sodium nitroprusside in the guinea-pig vas deferens.

Animals↗

Atrial natriuretic peptide and sodium nitroprusside stimulate cyclic GMP accumulation by avian skin fibroblasts and epiphyseal growth-plate chondroprogenitor cells.

Chondroprogenitor cells derived from avian tibia epiphyseal growth plate, and skin fibroblasts were cultured in vitro. In the fibroblasts, human (1-28) and rat (5-28) atrial natriuretic peptide (ANP) stimulated cyclic GMP (cGMP) production in a dose-dependent manner without affecting cAMP. Sodium nitroprusside also stimulated cGMP accumulation by chondroprogenitor cells and fibroblasts, but the maximum cGMP accumulation elicited by sodium nitroprusside was much lower than that obtained with ANP. The effects of ANP and sodium nitroprusside on chondroprogenitor cells and skin fibroblasts were additive. Human ANP increased cGMP production by the particulate fraction prepared either from chondroprogenitor cells or fibroblasts. Sodium nitroprusside, at concentrations of up to 1 mmol/l, did not affect cGMP production by the particulate fraction prepared from either cell type. The present study provides additional evidence that avian growth-plate chondroprogenitor cells and skin fibroblasts are targets for ANP. ANP and nitroprusside activate different guanylate cyclase isoenzymes--the particulate and soluble forms of the enzyme respectively. The data suggest that most of the guanylate cyclase activity in these cells is localized in the particulate fraction.

1-Methyl-3-isobutylxanthine↗

Augmented peritoneal mass transport with intraperitoneal nitroprusside.

Lightly restrained, alert New Zealand white rabbits underwent peritoneal dialysis by percutaneous instillation of standard dialysis solution with or without intraperitoneal nitroprusside. Corrected to a mean intraperitoneal dwell time of 36 minutes, mean clearances of creatinine and urea were 0.74 and 0.90 ml/kg/min in six rabbits. With intraperitoneal nitroprusside, 1.13 mg/kg clearances increased to 1.13 and 1.30 ml/kg/min (p less than 0.01) respectively. The 53% increment in creatinine clearance maintained the ratio clearance larger/smaller solute suggesting increased peritoneal permeability and/or area. Lower nitroprusside doses were less effective and not significantly above control. Nitroprusside also increased clearances during hypertonic peritoneal dialysis, but had no effect on osmotically induced water flux. Lavage studies demonstrated a persistent effect of nitroprusside after a single exposure and a sustained effect with repeated use.

Animals↗

Effect of alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) on the potency of sodium nitroprusside and nitroglycerine to decrease blood pressure in rats: a dose-response study.

The nitrovasodilators, sodium nitroprusside and nitroglycerine, effect a dose-dependent decrease in mean arterial blood pressure (MABP) by liberating nitric oxide. Alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) is known to bind nitric oxide. We studied the effect of DCLHb on the potency of sodium nitroprusside (n=36) and nitroglycerine (n=36) to decrease MABP in rats which received 1, 10, 100, 1,000, or 10,000 mg/kg of the DCLHb, or normal saline as the Control. Six doses of sodium nitroprusside or nitroglycerine were given to each rat in a systematically varied sequence. For both drugs, in rats given 1, 10, or 100 mg/kg of DCLHb there were no between groups differences in the change in MABP compared to the Control group. For rats that received 1,000 or 10,000 mg/kg of DCLHb, the potency of nitroglycerine and sodium nitroprusside to decrease MABP was less (p<0.05) than the other groups. These data support the hypothesis that small doses of DCLHb effect a minimal change in the potency of nitrovasodilators to reduce blood pressure. However, they suggest that clinically relevant doses of DCLHb attenuate the vasodilatory ability of sodium nitroprusside and nitroglycerine.

Animals↗

[Studies on the metabolism and distribution of 14C-sodium nitroprusside in rats (author's transl)].

Studies on the in vivo degradation of 14C-labelled nitroprusside (NP) were conducted in rats and indicated that the primary product was cyanide and not thiocyanate. With the administration of higher doses of sodium nitroprusside (NNP; Nipruss) cyanide, thipcyanate, Fe++ and Fe+++ were evident in the blood plasma, whereas [Fe(CN)6]4- and [Fe(CN)6]3- were not detected. The biological half-life for the disappearance of nitroprusside was about 2 min with a dose of 0.4 mg NNP/kg and was 28 min with a dose of 6.25 mg NNP/kg. Nitroprusside and its degradation products, cyanide and thiocyanate, were eliminated mainly in the urine. Significant accumulation of nitroprusside did not occur either in blood vessel walls, in smooth muscles, or in parenchymal organs.

Animals↗

[Effects of nitroprusside and vibration on peritoneal transport of solutes in continuous ambulatory peritoneal dialysis patients].

To explore the relationship between peritoneal transport of solutes and permeability of the peritoneum capillary as well as peritoneal stagnant fluid layer within dwell time, we observed the effects of nitroprusside and vibration on peritoneal transport of solutes in continuous ambulatory peritoneal dialysis(CAPD) patients. Twelve stable, routine CAPD patients were involved, who had no peritonitis for at least 4 weeks before the test. Standard peritoneal equilibrium tests(PETs) were performed, and mass transfer area coefficiency(MTAC) were calculated after adding nitroprusside to the dialysate or vibrating the patients's peritoneum. The concentrations of total protein, albumin and immunity globulin G in total drained dialysate were examined, and total drained volumes were recorded. Compared with the control, the MTACs value of BUN, Creatinine(Cr) increased significantly both in the nitroprusside group and vibration group(P < 0.05); the concentration of immunoglobin G in the total drained fluid was higher in the nitroprusside group than that in the control(P < 0.05); However, there was no significant difference in the total drained volume among the three groups. We conclude that nitroprusside and vibration can increase the peritoneal transport of small molecular solutes, and vibration has less influence on the loss of protein in CAPD. It suggests that moderated movement may improve the removal of the small molecules in CAPD patients.

Adult↗

Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine.

Sodium nitroprusside, nitroglycerin, sodium azide and hydroxylamine increased guanylate cyclase activity in particulate and/or soluble preparations from various tissues. While sodium nitroprusside increased guanylate cyclase activity in most of the preparations examined, the effects of sodium azide, hydroxylamine and nitroglycerin were tissue specific. Nitroglycerin and hydroxylamine were also less potent. Neither the protein activator factor nor catalase which is required for sodium azide effects altered the stimulatory effect of sodium nitroprusside. In the presence of sodium azide, sodium nitroprusside or hydroxylamine, magnesium ion was as effective as manganese ion as a sole cation cofactor for guanylate cyclase. With soluble guanylate cyclase from rat liver and bovine tracheal smooth muscle the concentrations of sodium nitroprusside that gave half-maximal stimulation with Mn2+ were 0.1 mM and 0.01 mM, respectively. Effective concentrations were slightly less with Mg2+ as a sole cation cofactor. The ability of these agents to increase cyclic GMP levels in intact tissues is probably due to their effects on guanylate cyclase activity. While the precise mechanism of guanylate cyclase activation by these agents is not known, activation may be due to the formation of nitric oxide or another reactive material since nitric oxide also increased guanylate cyclase activity.

Animals↗

Comparison of nicardipine and sodium nitroprusside in the treatment of hypertension after coronary bypass surgery (a pilot study).

Sodium nitroprusside is widely used in the treatment of hypertension after coronary artery bypass surgery despite its toxicity and its deleterious effect on the coronary circulation. The aim of this study was to compare the safety and effectiveness of nicardipine with sodium nitroprusside in a randomized study. Nicardipine and sodium nitroprusside are effective for controlling hypertension after coronary artery surgery. Oxygen myocardial balance was more often improved by nicardipine than by sodium nitroprusside. Hemodynamic stability was better with nicardipine which was also devoid of toxicity and might therefore have advantages over sodium nitroprusside in the management of hypertension after coronary artery surgery.

Aged↗

Mechanism of atrial natriuretic polypeptide and sodium nitroprusside-induced relaxation in guinea-pig tracheal smooth muscle.

Atrial natriuretic polypeptide (ANP) is composed of a family of peptides isolated from rat and human atria. In the present study, the relaxant effects of ANP, sodium nitroprusside and 8-bromo-cyclic guanosine monophosphate (GMP) were investigated in guinea-pig tracheal smooth muscle, and the tissue cyclic GMP and cyclic adenosine monophosphate (AMP) concentrations were measured. ANP, sodium nitroprusside and 8-bromo-cyclic GMP showed relaxant effects on the spontaneous tone in normal Krebs solution (5.9 mmol/l K(+)-2.4 mmol/l Ca++ solution). They diminished relaxant effects on 40 mmol/l K(+)-0.1 mmol/l Ca++ induced contraction, which was approximately the same tension as the spontaneous tone. Sodium nitroprusside and 8-bromo-cyclic GMP diminished less relaxant effects on 40 mmol/l K(+)-2.4 mmol/l Ca++ induced contraction, but ANP showed no relaxation. The tissue cyclic GMP levels following administration of ANP and sodium nitroprusside in normal Krebs solution, in 40 mmol/l K(+)-2.4 mmol/l Ca++ solution, and in 40 mmol/l K(+)-0.1 mmol/l Ca++ solution increased dose-dependently without regard to external Ca++ concentrations, while the tissue cyclic AMP levels did not change. These results suggest that ANP might be a novel potent relaxant in airway smooth muscle and the relaxant effect may be, at least in part, mediated by cyclic GMP. There was a difference in relaxant effects on tracheal smooth muscle between ANP and sodium nitroprusside.

8-Bromo Cyclic Adenosine Monophosphate↗

Specific effects of nitroprusside on myocardial O2 balance following coronary ligation in the dog heart.

The effect of gradual infusion of nitroprusside was studied in healthy and in ischemic hearts. In two areas of the left ventricular surface (ischemic and non-ischemic) local coronary blood flow was measured by a thermistor technique. Isometric contractile tension was recorded with strain gauge arches, and nicotinamide-adenine-dinucleotide (NADH) redox state was measured simultaneously in both regions using a two-channel fluorometer. Aortic blood pressure was also recorded. It was found that at an infusion rate of 1.0 microgram/kg/min, nitroprusside increased regional coronary blood supply in the healthy heart as well as in the ischemic and nonischemic areas of left anterior descending artery (LAD)-ligated hearts. Flow elevation was similar in all regions (37.0 +/- 6.1, 42.5 +/- 13.5 and 45.36 +/- 14.8%, respectively). At higher doses, a decrease of 6-10% in blood pressure had a detrimental effect on the coronary flow to the ischemic region without reducing flow to the nonischemic region. The NADH redox level was not significantly improved by nitroprusside in spite of elevated coronary blood supply to all regions examined. Moreover, higher doses of nitroprusside resulted in a significant elevation in NADH levels that could be correlated to the decrease in blood pressure. It is concluded that the effect of nitroprusside on coronary blood supply and myocardial O2 balance may be strongly dependent on the magnitude of its effect on blood pressure.

Animals↗

Effects of pimobendan on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy: comparison with nitroprusside.

The influence of pimobendan and nitroprusside on hemodynamics was investigated in nine patients with idiopathic dilated cardiomyopathy (NYHA class II-III). Pimobendan and nitroprusside resulted in a comparable decrease of left ventricular end-diastolic wall stress (preload) by 46% (p less than 0.01) and 52% (p less than 0.01), respectively, and of end-systolic wall stress (afterload) by 36% (p less than 0.01) and 34% (p less than 0.01), respectively. Cardiac index increased from 3.2 +/- 0.4 to 4.2 +/- 0.8 L/min/m2 with pimobendan (p less than 0.01) and did not significantly change with nitroprusside (3.0 +/- 0.6 L/min/m2). Compared to nitroprusside, pimobendan resulted in a significant increase in stroke volume index by 37% (p less than 0.01) and maximum rate of left ventricular pressure rise by 23% (p less than 0.05). Heart rate did not significantly change with either drug. Following the application of pimobendan, there was a decrease in myocardial oxygen consumption from 14.3 +/- 5.1 to 10.6 +/- 3.8 ml/min/100 g (p less than 0.05). The ratio of myocardial oxygen consumption and systolic stress-time integral did not significantly change. Thus, in comparison with nitroprusside, pimobendan exhibits significant inotropic and vasodilating properties. The hemodynamic actions of pimobendan are associated with favorable effects on myocardial energetics.

Adult↗

Comparative renal effects of intravenous administration of fenoldopam mesylate and sodium nitroprusside in patients with severe hypertension.

We studied the renal effects of intravenous administration of fenoldopam mesylate, a dopamine-1 agonist, vs sodium nitroprusside following acute reduction of blood pressure (BP) in 11 patients with severe hypertension (supine BP, 168/124 to 252/135 mm Hg). Following randomization (open-label), timed urinary and plasma samples for clearance of urea and creatinine and excretion of sodium, potassium, and calcium were obtained as well as plasma renin activity for a two-hour collection prior to infusion, during a two-hour period of BP control (supine diastolic BP, 95 to 110 mm Hg), and following two hours off the drugs. Mean arterial pressure was lowered similarly with the two drugs (-22% on fenoldopam vs -20% on nitroprusside; P = NS), and neither plasma renin activity nor plasma aldosterone concentration were changed by either drug. However, patients receiving fenoldopam had significant increases in urinary flow and excretion of sodium, potassium, and calcium, whereas patients receiving nitroprusside had no changes in these parameters. Patients receiving fenoldopam had a net fluid balance of -334 mL from the end of baseline to the end of the treatment period, while the nitroprusside group had a positive balance of 382 mL. Thus, these findings show that acute BP reduction with fenoldopam is associated with both a diuresis and natriuresis in severely hypertensive patients while lowering BP with nitroprusside does not predictably alter renal function and causes a moderate expansion in volume.

Adult↗