Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that platelets of patients with variant angina exhibited pronounced hyperactivity to epinephrine, as assessed by aggregation study. To determine whether this is associated with a change in surface alpha-adrenoceptor status, we investigated the capacity and affinity of binding sites for [3H]dihydroergocryptine, a potent alpha-antagonist, of platelet lysates prepared from 22 patients with ischemic heart disease and 13 control subjects of similar age. [3H]DHE binding capacity to platelets from control subjects, 6 patients with acute myocardial infarction, 9 with effort angina and 7 with variant angina were 233 +/- 44 (SD), 226 +/- 53, 252 +/- 58 and 348 +/- 48 fmol/mg protein and its affinity were 2.05 +/- 1.40, 0.98 +/- 0.46, 1.59 +/- 0.37 and 1.49 +/- 0.66 nM, respectively. The patients with variant angina had significantly higher capacity of platelet alpha-adrenoceptor than controls (49% increase) or patients with other types of ischemic heart disease. In contrast, the affinity for [3H]DHE was not significantly different as compared with other three groups. Similar increments in the binding capacity for [3H]-rauwolscine, alpha 2 antagonist, were found in platelet lysates prepared from 6 patients with variant angina. These results suggest that increased capacity of platelet alpha-adrenoceptor may explain enhanced reactivity to epinephrine in patients with variant angina.
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PMID:Alpha 2-adrenoceptors and platelet function in patients with variant angina. 257 2

Organic nitrates, such as nitroglycerin (NTG), have been used to relieve the symptoms of angina pectoris. However, their biochemical mechanisms of action, particularly in relation to the development of tolerance, are incompletely defined. It has been reported that supplemental antioxidants such as vitamin E attenuate the development of nitrate tolerance. Therefore, we examined the role of vitamin E in the regulation of nitrate tolerance. Continuous NTG infusion induced nitrate tolerance in rats after 48 h, and vitamin E concentrations decreased in a time-dependent manner in tissues and plasma. Vitamin E supplementation (0.5 g/kg diet) maintained higher concentrations of vitamin E during NTG infusion. The onset and extent of the tolerance, estimated by the decrease in blood pressure following NTG bolus injection during the infusion of NTG, were accentuated in the vitamin E-deficient group. Vitamin E supplementation inhibited nitrate tolerance 48 h after NTG infusion. Cardiac P450 expression (CYP1A2) assessed by immunoblotting, markedly decreased 48 h after NTG administration in control rats. The supplementation of vitamin E significantly attenuated the decrease in P450. Treatment of NTG enhanced vascular superoxide production (L-012 chemiluminescence, DHE fluorescence). The peak of lipid peroxidation and free radical generation in the heart was reached before tolerance developed. In contrast, vitamin E-deficient hearts had lower P450 expression and higher free radical generation than control hearts. To evaluate other vitamin E-inhibitable mechanisms of nitrate tolerance, we studied the NO-cGMP pathway. NTG markedly reduced the vasodilator-stimulated phosphoprotein (VASP) serine 239 phosphorylation (specific substrate of cGMP-activated protein kinase I; cGK-I) in tolerant hearts. Vitamin E inhibited the depletion of pVASP. In conclusion, because continuous NTG infusion causes vitamin E depletion as well as nitrate tolerance, vitamin E deficiency may further accelerate nitrate tolerance via an increase in oxidative stress, the reduced bioconversion because of decreased P450 expression, and impairment of the NO/cGMP pathway in tolerant heart tissues.
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PMID:Vitamin E deficiency accelerates nitrate tolerance via a decrease in cardiac P450 expression and increased oxidative stress. 1652 Feb 33