Drugs online research references
J Cardiovasc Pharmacol. 1998 Jun;31(6):963-70.
Cardiovascular effects of nepicastat (RS-25560-197), a novel dopamine beta-hydroxylase inhibitor.
Stanley WC, Lee K, Johnson LG, Whiting RL, Eglen RM, Hegde SS.
Neurobiology Unit, Center for Biological Research, Roche Bioscience, Palo Alto, California 94304, USA.
Nepicastat (RS-25560-197) is a novel, selective, and potent inhibitor of dopamine beta-hydroxylase, which modulates catecholamine levels (reduces norepinephrine and elevates dopamine) in cardiovascular tissues. This study was designed to evaluate the cardiovascular effects of nepicastat. Acute oral administration of nepicastat (0.3, 1, 3, 10, and 30 mg/kg) produced attenuation of the pressor and positive chronotropic responses to preganglionic sympathetic nerve stimulation (about twofold to sixfold shift in the frequency-response curve) in pithed spontaneously hypertensive rats (SHRs). In inactin-anesthetized SHRs, the antihypertensive effects of nepicastat (3 mg/kg, i.v.) were accompanied by a significant decrease in renal vascular resistance (38%), a tendency toward an increase in renal blood flow (22%), and no adverse effects on urine output and Na/K excretion. In conscious, unrestrained, telemetry-implanted SHRs, nepicastat (30 and 100 mg/kg/day for 30 days) produced dose-dependent decreases in mean arterial blood pressure (peak decrease of 20 and 42 mm Hg, respectively) without evoking reflex tachycardia. Long-term, concurrent administration of nepicastat (30 mg/kg/day, p.o.) and a subthreshold dose of enalapril (1 mg/kg/day, p.o.) produced greater antihypertensive effects than those produced by nepicastat alone. In normal dogs, nepicastat (5.0 mg/kg, p.o., b.i.d., for 4.5 days) blunted the positive chronotropic and pressor response to tyramine. These findings suggest that nepicastat functionally modulates sympathetic drive to cardiovascular tissues and may be of value in the treatment of cardiovascular disorders associated with overactivation of the sympathetic nervous system such as hypertension and congestive heart failure.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9641484&dopt=Abstract
Am J Physiol. 1998 Jun;274(6 Pt 2):R1718-24.
Urinary acidification and net acid excretion in adult rats treated neonatally with enalapril.
Guron G, Marcussen N, Friberg P.
Department of Physiology, Institute of Physiology and Pharmacology, Goteborg University, S413-90 Goteborg, Sweden.
Neonatal blockade of the renin-angiotensin system in rats induces irreversible renal histological abnormalities, including papillary atrophy and an impaired urinary concentrating ability. The aim was to investigate urinary acidification and net acid excretion in adult Wistar rats treated neonatally with enalapril (10 mg . kg-1 . day-1) or vehicle from 5 to 24 days of age. Analyses were performed in both metabolic balance studies and renal clearance experiments performed under pentobarbital sodium anesthesia. There were no differences between groups in urine pH or urinary excretion rates of bicarbonate, titratable acid, or ammonium, neither during control conditions nor after chronic NH4Cl loading (assessed before and after Na2SO4 infusion). Glomerular filtration rate, maximal tubular bicarbonate reabsorption, and the urine-to-blood PCO2 gradient in alkaline urine during NaHCO3 infusion did not differ between groups. Neonatally enalapril-treated rats showed a urine concentration defect and papillary damage. In conclusion, neonatal enalapril treatment produces a differentiated abnormality in tubular function in which urine concentration is impaired but urinary acidification and net acid excretion are intact.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9841484&dopt=Abstract
Ter Arkh. 1996;68(4):54-7.
[The activity of the neurohumoral regulatory systems, the status of the electrolyte balance and the clinical efficacy of Renitec in hypertension patients]
[Article in Russian]
Ol'binskaia LI, Pinskaia EV, Bol'shakova TD, Anastas'ina GV, Tiabenkova VF.
Hypotensive effect of renitek (enalapril maleate) was assessed by activity of some neuroregulation systems and electrolyte balance in 16 patients with essential hypertension (EH). Maximal time of treatment for the assessment was 14 days. Renitek in a single dose 20-40 mg/day produced a response in 80% of EH stage II patients with low activity of plasma renin (PR). A hypotensive effect of the drug proved more essential in patients with higher baseline urinary excretion of aldosterone, adrenaline, noradrenaline and sodium. This effect is associated with stimulation of PR activity, urinary excretion of sodium, reduction in plasma and 24-h urine of aldosterone, adrenaline and noradrenaline concentrations. Renitek nonresponders exhibited high aldosterone concentration in plasma and its normal excretion with urine, diminished sodium excretion with urine. After 2 weeks of treatment blood and urine hormones were close to the initial levels while sodium excretion with urine went down.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9324794&dopt=Abstract
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