Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Remikiren is an orally available renin inhibitor with an established blood pressure-lowering effect in patients with essential hypertension. No data are available on the renal effects of remikiren in humans. We therefore studied the effects of a single oral administration of remikiren on blood pressure and renal function in 16 patients with essential hypertension on a restricted dietary sodium intake. Remikiren induced a peak fall in mean arterial pressure of 8.5 +/- 0.8%. The glomerular filtration rate (GFR) remained stable, whereas the effective renal-plasma flow rose by 11.3 +/- 1.4%. As a consequence, the filtration fraction and the renal vascular resistance fell by 11.7 +/- 1.2% and 17.6 +/- 1.3%, respectively. These systemic and renal hemodynamic changes were more pronounced in individuals with a higher initial immunoreactive renin. Remikiren induced a significant rise in the fractional excretion of sodium [0.38% (0.24-0.52) to 0.50% (0.31-0.76)] and lithium [28.7% (25.0-32.4) to 33.2% (27-39.4)]. Moreover, remikiren induced a decrease in urinary albumin excretion [497 (268-815) to 252 (114-389) micrograms/h]. In patients with essential hypertension, a single oral dose of remikiren can induce a renal vasodilation, without affecting the GFR and despite a significant decrease in blood pressure. This systemic and renal hemodynamic response is more pronounced in case of a more activated renin-angiotensin system.
 ...
PMID:Renal and systemic effects of the renin inhibitor remikiren in patients with essential hypertension. 756 63

The objective of this study was to assess the antihypertensive efficacy of the new renin inhibitor Ro 42-5892 in patients with essential hypertension treated with 100 mg once daily orally. This was a double-blind, placebo-controlled, parallel group trial. After three weeks of wash-out and one week of single-blind placebo run-in periods, 25 patients with mild to moderate essential hypertension (sitting DBP between 95 and 114 mmHg) were randomised to receive either placebo (n = 12) or 100 mg of Ro 42-5892 (n = 13) once daily for eight days. On the eighth day, four hours after the oral administration, patients were randomised to receive intravenously either placebo or 10 mg of Ro 42-5892. BP and heart rate were measured repeatedly (hourly for eight hours and at the 24th hour post-dose) on the first and last days of active treatment. Compared with the placebo group, a slight decrease in sitting DBP was observed after the first dose in the Ro 42-5892 group. The decrease in sitting DBP reached significant levels only at six to eight hours post-dosing. In contrast, on the last day of active treatment, a larger, faster and longer decrease in sitting DBP was observed in the Ro 42-5892 group. Thus, the peak effect (-8.9 +/- 1.9 vs. -2.9 +/- 1.3 mmHg, P < 0.01) was reached 1.5 hours post-dosing and the trough effect (24 hours post-dosing) was slightly but significantly lower when compared with the placebo group (-3.0 +/- 1.0 vs -0.3 +/- 0.8 mmHg, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Time dependency of the antihypertensive efficacy of the new renin inhibitor Ro 42-5892. 820 39

The efficacy of multiple oral administration of the renin inhibitor Ro 42-5892 [(S)-alpha-](t-butylsulfonyl)-methyl]hydrocinnamamido]-N-[1S , 2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]-imi dazole-4- propionamide] was studied. Forty-nine patients with moderate essential hypertension were randomly assigned to three groups that entered an 8-day double-blind oral treatment period: daily administration of placebo (group A), 300 mg Ro 42-5892 (group B), or 600 mg Ro 42-5892 (group C). Four hours after the last oral drug intake, placebo was administered intravenously to subjects in group A and 100 mg Ro 42-5892 was administered intravenously to subjects in groups B and C. Sitting systolic and diastolic blood pressures were measured on days 1 and 8 with a blood pressure device. On day 1, systolic blood pressure maximally decreased by 13.3 +/- 9.3, 20.2 +/- 11.2, and 24.1 +/- 11.3 mm Hg in groups A, B, and C, respectively (mean +/- SD; p < 0.01 for group A versus group C). Diastolic blood pressure maximally decreased 9.4 +/- 5.7, 13.9 +/- 8.7, and 11.8 +/- 5.7 mm Hg (difference not significant). On day 8, systolic blood pressure maximally decreased 19.5 +/- 16.5, 26.5 +/- 17.4, and 30.5 +/- 18.4 mm Hg and diastolic blood pressure maximally decreased 14.8 +/- 5.0, 16.2 +/- 9.0, and 17.9 +/- 12.7 mm Hg (difference not significant) compared with pretreatment values. Intravenous drug administration did not further reduce blood pressure, suggesting that the mode of action and not the low bioavailability was the limiting factor for the low efficacy.
 ...
PMID:Efficacy and tolerability of the renin inhibitor Ro 42-5892 in patients with hypertension. 822 99

Newly developed IRMAs to measure the plasma concentrations of renin and prorenin were validated for clinical use and compared with a classical enzyme kinetic assay. The IRMAs involve two monoclonal antibodies, one that reacts equally well with renin and prorenin and one that recognizes renin well but prorenin only minimally. Prorenin reactivity with the second antibody was enhanced by adding the renin inhibitor, Remikiren, to plasma. The complex of prorenin with this active-site ligand undergoes a conformational change, whereby prorenin is converted into a form that cannot be differentiated from renin by the IRMA. The linear working range of the assay was 4.0-3000 mU/L. The concentration of prorenin was calculated by subtracting the assay result obtained without Remikiren (i.e., renin) from the result obtained with Remikiren (i.e., renin plus prorenin). No more than 2% of prorenin present in plasma was detected as renin. The interassay CVs for renin quantification were 18%, 13%, and 8% at low, medium, and high concentrations, respectively. The interassay CV for calculated prorenin was 8% at both low and high concentrations. The IRMA results were highly correlated with those of an enzyme kinetic assay in healthy subjects; in patients with such conditions as primary hyperaldosteronism, renovascular hypertension, and low-, medium-, and high-renin essential hypertension; and in women undergoing gonadotropin stimulation.
 ...
PMID:Clinical validation of renin monoclonal antibody-based sandwich assays of renin and prorenin, and use of renin inhibitor to enhance prorenin immunoreactivity. 867 11

Remikiren (Ro 42-5892) is a new orally active renin inhibitor with high potency and specificity in vitro. In the present study, the drug was given in a short-term study in patients with essential hypertension, either as monotherapy or with added hydrochlorothiazide. Following a wash-out period of at least 3 weeks and then 8 days of single-blind placebo, 29 patients with essential hypertension were given remikiren 600 mg orally for 8 days. After 4 days of remikiren, hydrochlorothiazide 12.5 mg or 25 mg or placebo was added in double-blind fashion for the last 4 days. There were no significant changes in blood pressure in patients given remikiren alone. In patients given additional hydrochlorothiazide for 4 days, a marked reduction in blood pressure was observed. Remikiren effectively inhibited the plasma renin activity 24 h post-dose, whereas angiotensin II was reduced only during the first hours after drug administration. It is concluded that remikiren is orally effective. Its antihypertensive effect during short-term administration was not significant, but when given with a diuretic, a marked potentiation occurred. Further studies are needed to establish the long-term effects of remikiren alone and in combination therapy.
 ...
PMID:Remikiren (Ro 42-5892)--an orally active renin inhibitor in essential hypertension. Effects on blood pressure and the renin-angiotensin-aldosterone system. 878 74