Disease relevance of Bay k 5552

• CONCLUSIONS: In this population of patients with diabetes and hypertension, we found a significantly higher incidence of fatal and nonfatal myocardial infarction among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril [1].
• Nisoldipine and myocardial infarction [2].
• Intracellular calcium and ventricular function. Effects of nisoldipine on global ischemia in the isovolumic, coronary-perfused heart [3].
• In this placebo-controlled, parallel-design study, the dose-response relation of monotherapy with nisoldipine administered twice daily was studied in patients with stable angina pectoris [4].
• After nisoldipine administration, chest pain was not induced in 13 of 19 patients and was of lessened severity in five patients with the same work load as those performing control exercise [5].

Psychiatry related information on Bay k 5552

• Patients in the moderate therapy group were given placebo, while the patients randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication [6].
• 5. In conclusion nisoldipine, as well as other calcium antagonists, may have a place in the treatment of some mood disorders [7].

High impact information on Bay k 5552

• Using a multiple logistic-regression model with adjustment for cardiac risk factors, we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infarctions (a total of 24) than enalapril (total, 4) (risk ratio, 9.5; 95 percent confidence interval, 2.7 to 33.8) [1].
• On day 1, pigs received an i.v. infusion of a combination of antioxidants (superoxide dismutase, catalase, and N-2 mercaptopropionyl glycine; group II, n = 9), nisoldipine (group III, n = 6), or vehicle (group I [controls], n = 9) [8].
• Double-blind, dose-response, placebo-controlled multicenter study of nisoldipine. A new second-generation calcium channel blocker in angina pectoris [4].
• However, four patients developed unstable angina while on nisoldipine therapy (two in the 2.5-mg, one in the 5-mg, and one in the 10-mg-b.i.d. group) and two patients died suddenly in the nisoldipine 10-mg-b.i.d. group [4].
• However, coronary sinus flow at peak exercise increased significantly from 219 +/- 24 to 249 +/- 31 ml/min (p less than 0.01) after nisoldipine, and myocardial oxygen uptake was not significantly changed despite decreased coronary vascular resistance [5].

Chemical compound and disease context of Bay k 5552

• This response was inhibited by hirudin and nisoldipine, but not by propranolol, prazosin, or pretreatment with pertussis toxin [9].
• Group III hearts were pretreated with nisoldipine (1 microgram/min) for 5 minutes before ischemia, and group IV hearts were treated with nitroglycerin (93 micrograms/min) before and after ischemia to mimic the vasodilation caused by nisoldipine [10].
• In 12 rats bearing Walker 256 carcinomas i.p. injection of 0.2-0.4 mg/kg nisoldipine caused a reduction in the tumor-to-muscle flow relationship of 4.4 +/- 1.9 (SD) to 1.74 +/- 0.86 as determined by intraarterial 133Xe injection; i.p. injection of 2-8 mg/kg 5-HT (N = 13) caused a respective reduction from 3.9 +/- 2.67 to 1.3 +/- 1.59 [11].
• Albuminuria was reduced 47% (95% CI 21-65) in the lisinopril group versus an increase of 11% (-3 to 27) in the nisoldipine group (P = 0.001) [12].
• The effects of the addition of slow-release nifedipine 20 mg twice daily and nisoldipine 10 mg twice daily to atenolol monotherapy were compared in a double-blind placebo-controlled study of 24 patients with chronic stable angina pectoris [13].

Biological context of Bay k 5552

• The protective effect of treatment with nisoldipine appeared to be independent of vasodilation [10].
• Effects on action potential duration are occluded by 1 microM nisoldipine, which specifically blocks calcium channels [14].
• In contrast, nisoldipine had no effect on skinned muscle contractions, although it inhibited, almost completely, the contraction of intact muscle at concentrations below 10(-6) M [15].
• There were differences in regional blood flow; during coronary artery occlusion, nisoldipine increased blood flow significantly in the endocardium and epicardium of nonischemic and ischemic zones [16].
• Mean arterial blood pressure (24 h) was reduced from (mean +/- SE) 108 +/- 3 mmHg at baseline to 101 +/- 2 in average during treatment in the lisinopril group and from 105 +/- 2 to 103 +/- 2 in the nisoldipine group (P = 0.06 comparing changes in the two groups) [12].

Anatomical context of Bay k 5552

• Single nisoldipine-sensitive calcium channels in smooth muscle cells isolated from rabbit mesenteric artery [17].
• Thus, in the conscious baboon, nisoldipine administered 1 hour after coronary artery occlusion exerted a marked effect in diminishing reperfusion-induced arrhythmias and improved blood flow to the ischemic zone during occlusion but did not salvage ischemic tissue [16].
• This study was designed to afford direct viewing of the effects of myocardial ischemia-reperfusion on the coronary microcirculation and to determine whether pretreatment with the calcium blocker nisoldipine would attenuate any microvascular damage during reperfusion [10].
• Nifedipine and nisoldipine blocked bag cell Ca2+ currents with effects similar to those seen previously on Ca2+ currents in cardiac muscle: both compounds appeared to interact with Ca2+ channels when they were closed, open, and inactivated [18].
• We thus conclude that the more potent nisoldipine inhibition of smooth muscle versus cardiac L-type Ca2+ channels is not attributable to differences in channel inactivation or activation [19].

Associations of Bay k 5552 with other chemical compounds

• Effects of a chronic treatment by nisoldipine, a calcium antagonistic dihydropyridine, on arteries of spontaneously hypertensive rats [20].
• Alternans of both action potential shape and APD was suppressed by nisoldipine (2 X 10(-6) M) and attenuated by Bay K 8644 (3 X 10(-8) M) [21].
• NFAT4 activation by PDGF depends on Ca(2+) entry through voltage-dependent Ca(2+) channels, because its nuclear accumulation is prevented by the Ca(2+) channel blocker nisoldipine and the K(+) channel opener pinacidil [22].
• Patients are also randomized to nisoldipine or enalapril, with open-label medications added if further blood pressure control is necessary [23].
• Verapamil, nisoldipine and nimodipine were all effective inhibitors of constriction by either route of administration, and in doses having little or no dilating action [24].

Gene context of Bay k 5552

• The effect of the calcium antagonist, nisoldipine, on ET-1 levels has also been examined in cultured IMA endothelial cells (IMAEC) [25].
• Effects of nisoldipine on endothelin-1- and angiotensin II-induced immediate/early gene expression and protein synthesis in adult rat ventricular cardiomyocytes [26].
• To investigate the effect of antihypertensive treatment on insulin sensitivity and fasting adiponectin serum levels, 37 nondiabetic patients with essential hypertension were randomized to receive telmisartan, the calcium channel blocker nisoldipine, or their combination for 6 weeks in a prospective, parallel group study [27].
• Therefore, nisoldipine may influence the signal transduction pathway, i.e., through PKC [26].
• It exacerbated the reperfusion ventricular fibrillation, reduced the activities of superoxide dismutase and catalase and increased the contents of malondialdehyde in Langendorff heart of rats. m-Nisoldipine or nisoldipine (0.05 mumol/L) was perfused 10 min prior to coronary artery ligation until the end of the experiment [28].

Analytical, diagnostic and therapeutic context of Bay k 5552

• Nisoldipine significantly accelerated the decline in [Ca2+]i during reperfusion and improved recovery of contractility and relaxation [3].
• Nisoldipine or placebo was administered twice daily for 4 weeks and symptom-limited exercise tests were repeated at 2 and 10-14 hours after the double-blind medication [4].
• The experimental group of animals (n = 7) was treated with the calcium channel blocker nisoldipine (0.1 microgram/kg/min) from 1 hour after coronary occlusion to 3 hours after coronary reperfusion [16].
• The effects of nisoldipine on regional myocardial perfusion and neuro-hormonal status were assessed in a double-blind, placebo-controlled study of 32 patients [29].
• Nisoldipine was administered as a 4.5 micrograms kg-1 intravenous bolus over 3 min followed by intravenous infusion of 0.2 microgram kg-1 min-1 during 60 min [30].

References