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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertensive diabetic rats develop a cardiomyopathy characterized by systolic and diastolic ventricular dysfunction, myocardial hypertrophy and fibrosis, pulmonary congestion and a very high mortality rate. Alterations in contractile proteins and sarcoplasmic reticular calcium (Ca2+) transport in diabetic myocardium and their partial reversal with verapamil suggest that calcium channel blockade may prevent death from congestive heart failure in hypertensive diabetic rats. A large group of rats with renovascular hypertension and streptozotocin diabetes were divided into four groups: untreated animals (Group 1) and animals treated with 100 (Group 2), 300 (Group 3) or 600 (Group 4) mg/kg per day of sustained release diltiazem mixed in their food. Treatment was begun shortly after the onset of hypertension and diabetes. Mortality rates after 4 months were 59% (19 of 32), 53% (17 of 32), 27% (7 of 26) and 35% (12 of 34) in Groups 1, 2, 3 and 4, respectively; the mortality rate in age-matched control rats was 5% (1 of 19). The reductions in mortality rates in Groups 3 and 4 were statistically significant. Diltiazem did not change systolic blood pressure, serum glucose concentration, heart rate or left ventricular mass. There was a trend to decreased left ventricular interstitial fibrosis and perivascular fibrosis in diltiazem-treated animals. Ventricular collagen concentration was similar in untreated hypertensive diabetic and control rats; levels were higher in hypertensive diabetic rats that died than in those that survived. There was a trend to decreased collagen concentration as diltiazem dose increased. Myosin isoenzyme distribution was not changed in Groups 3 and 4 (in comparison with Group 1). In all hypertensive diabetic groups, rats that died had a higher blood pressure, heart rate, relative left ventricular mass, lung weight and lung water than did survivors. The mortality rate was two to three times higher among rats with an initial blood pressure greater than or equal to 180 mm Hg. The beneficial effects of diltiazem on survival were most significant among rats with severe hypertension.
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PMID:Beneficial effects of diltiazem on the natural history of hypertensive diabetic cardiomyopathy in rats. 183 34

The effect of diltiazem on long-term outcome in patients with acute myocardial infarction with and without a history of systemic hypertension was investigated in 2,466 patients using the Multicenter Diltiazem Postinfarction Trial data-base. The baseline variables were comparable in the diltiazem and placebo-treated patients within the groups with and without hypertension. The initial 60-mg dose of diltiazem was associated with a significant (p less than 0.001) but modest (3%) reduction in blood pressure and heart rate in both groups with and without hypertension. Univariate and multivariate analyses revealed a meaningful overall reduction in first recurrent cardiac events (cardiac death or nonfatal reinfarction, whichever occurred first) and cardiac death in patients with hypertension treated with diltiazem compared with results in those treated with placebo. Similar effects were not observed in patients without a history of hypertension. When first recurrent cardiac events were used as the end point, the diltiazem:placebo hazard ratio (95% confidence limits) was 0.77 (0.58, 1.01) for the total hypertension group, and 0.67 (0.47, 0.96) and 1.32 (0.83, 2.10) for patients with hypertension with and without pulmonary congestion during the acute infarction, respectively. Similar results were observed using cardiac death as the end point. Beta blockers had a negligible effect on the hypertension-diltiazem relation. These findings suggest that diltiazem may exert a long-term beneficial effect in most patients with hypertension who do not have pulmonary congestion during an acute infarction, and a detrimental effect in the minority who have pulmonary congestion.
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PMID:Effects of diltiazem on long-term outcome after acute myocardial infarction in patients with and without a history of systemic hypertension. The Multicenter Diltiazem Postinfarction Trial Research Group. 187 66

Midaglizole (3 and 30 mg/kg, i.v.) increased blood pressure in pithed rats. The pressor response was not inhibited by intravenous prazosin (0.3 mg/kg), yohimbine (1 mg/kg), ketanserin (1 mg/kg) or diphenhydramine (5 mg/kg). Diltiazem (1 mg/kg) antagonized the hypertension. Idazoxan (10 mg/kg) also increased blood pressure, and the pressor response was inhibited by prazosin, but not by yohimbine. These results suggest that the vascular effect of midaglizole is due to a mechanism different from that of idazoxan.
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PMID:Intrinsic pressor activity of midaglizole, an alpha-2 adrenoceptor antagonist, in pithed rats. 197 44

Diltiazem, a Ca-channel blocker that is used clinically for the treatment of hypertension and cardiac arrhythmias, reduces the contractility of extraocular muscles. Exposure of rabbit extraocular muscle to diltiazem in vitro reduces the sustained tension that is generated by the tonic, multiply innervated fibers, and decreases the baseline, or resting, tension of the muscle. When diltiazem is injected into a selected extraocular muscle in the rabbit in vivo, it causes a temporary weakening of the muscle, which is indicated by a deviation of eye position. These in vivo effects are of short duration, are easily reproducible, and vary with dosage. The results of this study raise the possibility that diltiazem may be used as an alternative to the surgical treatment of strabismus and other oculomotor dysfunctions including blepharospasm.
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PMID:Diltiazem reduces the contractility of extraocular muscles in vitro and in vivo. 213 91

Diltiazem is a commonly prescribed calcium-channel antagonist for hypertension and ischemic heart disease. The incidence of rash associated with diltiazem therapy is reported to be 1.3 percent. We describe two patients who developed erythematous, macular skin eruptions, approximately two weeks following institution of diltiazem. The skin eruptions resolved after symptomatic treatment and the patients received further therapy with another calcium-channel antagonist. Diltiazem-associated skin eruptions are a rare adverse effect; however, the incidence of rash may occur more frequently than reported in postmarketing surveillance studies.
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PMID:Reports of erythematous macular skin eruptions associated with diltiazem therapy. 214 57

Diltiazem is a calcium antagonist effective in the treatment of stable, variant and unstable angina pectoris and mild to moderate systemic hypertension, with a generally favourable adverse effect profile. It is also effective in terminating supraventricular tachycardia and in controlling the ventricular response to atrial fibrillation/flutter. Atrioventricular block, the risk of which may be exacerbated by concomitant beta-adrenoceptor antagonist therapy, occurs rarely as an adverse effect of diltiazem treatment. Diltiazem appears to exert complex cardioprotective effects which have been of benefit after intracoronary administration to patients undergoing coronary angiography and bypass procedures. In addition, long term diltiazem treatment has produced a significant reduction in subsequent cardiac events in patients with non-Q wave myocardial infarction. Thus, diltiazem is an effective and well-tolerated first-line or alternative treatment of patients with ischaemic heart disease, systemic hypertension, and supraventricular arrhythmias, with possible potential in limiting ischaemia-induced myocardial damage.
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PMID:Diltiazem. A reappraisal of its pharmacological properties and therapeutic use. 219 51

Renin and catecholamine levels were determined in patients with mild to moderate hypertension before and after treatment with sustained release diltiazem or captopril and were correlated with the blood pressure response to these antihypertensives. Eight weeks of treatment with either agent led to equal decreases in both systolic and diastolic blood pressure. Pretreatment plasma renin activity (PRA) and plasma norepinephrine did not predict the blood pressure response to either agent. Diltiazem significantly increased both PRA and supine norepinephrine levels. However, in the diltiazem treated patients, there was no correlation between the change in plasma norepinephrine and the change in systolic or diastolic blood pressure. In contrast, there was a negative correlation (P less than .05) between the reactive rise in PRA and the decrease in systolic blood pressure. Thus, the antihypertensive response to a calcium channel blocker may be determined, in part, by the reactive response of pressor systems.
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PMID:Humoral factors determining the blood pressure response to converting enzyme inhibition and calcium channel blockade. 222 51

The purpose of the present study was to investigate the effects of a Ca2(+)-antagonist on vascular sympathetic nerve activity in salt-dependent hypertension. Isolated mesenteric vasculature preparations from reduced renal mass-salt hypertensive and age-matched normotensive control rats were used to examine the effects of diltiazem on vascular responsiveness and norepinephrine release from sympathetic nerve endings. Pressor responses and endogenous norepinephrine release during electrical nerve stimulation were significantly greater in preparations from salt-dependent hypertensive rats than from normotensive control rats. Diltiazem inhibited both stimulation-evoked pressor responses and norepinephrine release in a dose-dependent manner. The attenuation of these responses was more pronounced in preparations from rats with salt-dependent hypertension than in those from control rats. These results indicate that norepinephrine release from vascular adrenergic neurons is enhanced in the mesenteric vasculatures of rats with salt-dependent hypertension. The marked reduction of stimulation-evoked pressor responses and norepinephrine release by diltiazem suggests that enhanced Ca2(+)-dependent adrenergic transmission may contribute to the exaggerated vascular sympathetic tone in salt-dependent hypertension.
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PMID:Effects of a calcium-antagonist on vascular sympathetic nerve activity in salt-dependent hypertension. 223 65

The purpose of this study was to evaluate the effect of calcium antagonists on basal tension and the elevated 42K efflux in aorta from aldosterone-salt hypertensive rats. Diltiazem decreased the basal tension (2.0 +/- 0.4 g) as well as the phasic contractile activity and returned the elevated 42K efflux (0.018 +/- 0.002/min) toward control values (0.010 +/- 0.001/min, p less than 0.001). The diltiazem median inhibitory concentration (IC50) for basal tension (0.04 +/- 0.02 microM), however, was sevenfold less than the IC50 for basal 42K efflux (0.22 +/- 0.08 microM, p less than 0.01). The basal 45Ca influx in aorta from aldosterone-salt hypertensive rats (120 +/- 4 microM/l cell H2O/min) was also decreased by diltiazem in a concentration-dependent manner, whereas the 45Ca influx in aorta from control-salt rats (135 +/- 3 microM/l cell H2O/min) was not altered. Similarly, the dihydropyridine nisoldipine eliminated the basal tension (2.7 +/- 0.5 g) and returned the elevated basal 42K efflux from the hypertensive aorta toward control levels (0.010 +/- 0.0003/min, p less than 0.001). The nisoldipine IC50 for basal tension (0.016 +/- 0.01 nM) was 160-fold less than the IC50 for basal 42K efflux (1.8 +/- 1.2 nm, p less than 0.001). Neither diltiazem nor nisoldipine nisoldipine altered the basal 42K efflux or contractile activity of aorta from control-salt rats. These results suggest that the basal tension and elevated 42K efflux in aorta from aldosterone-salt hypertensive rats are supported by the entry of extracellular calcium into the tissue through potential-operated calcium channels.
Hypertension 1990 Jan
PMID:Calcium antagonists inhibit elevated potassium efflux from aorta of aldosterone-salt hypertensive rats. 229 15

This study investigated the effects of diltiazem (a Ca2(+)-entry blocker) on neuromuscular junctions of blood vessels in hypertension. In isolated perfused mesenteric vasculatures prepared from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY), the effects of diltiazem on norepinephrine release from vascular adrenergic neurons and pressor responses were examined. The influences of extracellular Ca2(+)-reduction on these responses were also studied. Stimulation evoked pressor responses and norepinephrine release were significantly greater in the mesenteric vasculatures of SHR than in those of WKY. Diltiazem inhibited both pressor responses and norepinephrine release during electrical nerve stimulation in a dose-dependent manner. The suppression of these responses was more pronounced in SHR than in WKY. Reduction of extracellular Ca2(+)-concentration also decreased the responses in SHR and WKY, and the inhibitory degree was significantly greater in SHR than in WKY. These results demonstrate that diltiazem affected the presynaptic site of the mesenteric vasculatures and decreased the stimulation-evoked norepinephrine release from vascular adrenergic neurons with a concomitant reduction of pressor responses of the preparation. Furthermore, the marked inhibition of pressor responses and norepinephrine release by diltiazem or Ca2(+)-depletion in SHR may suggest the increased Ca2(+)-dependency in vascular neurotransmission in this model of hypertension.
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PMID:Enhanced neuroinhibitory effect of diltiazem in blood vessels of spontaneously hypertensive rats. 236 95


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