Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.6 (CAD)
 4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated human coronary arteries are known to develop spontaneous phasic contractions (SPCs). The goal of the present study was to assess the role of endothelin (ET) in these contractions. Endothelium-denuded rings from left anterior descending (LAD) coronary arteries of patients with coronary artery disease (CAD; n = 3) undergoing cardiac transplantation developed SPCs within 1-2 h. The contractions were abolished by the ETA receptor antagonist BQ-123 or the mixed ET receptor antagonist bosentan (1 and 3 microM), whereas the contractions persisted for several hours in control rings. Exogenous ET-1 (10 pM) increased the amplitude of SPCs and initiated SPCs in rings that did not exhibit SPCs. Higher concentrations of ET-1 (> or = 1 nM) were able to re-induce SPC in rings in which SPCs had been abolished by BQ-123 or bosentan. These results suggest that ET plays an important role in spontaneous phasic contractions of isolated human coronary artery rings.
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PMID:Role of endothelin in spontaneous phasic contraction of human coronary arteries. 858 62

The purpose of this study was to investigate whether there are differences in the expression of the endothelin (ET) system in the peripheral vasculature of diabetic African-American (AA) and Caucasian (CA) patients. Tibial artery specimens were obtained from diabetic (MD = 8 and CAD = 5) and non-diabetic (AAND = 6 and CAND = 5) patients undergoing lower limb amputation. The gene expression of ET-1 precursor (PPET-1), ET(A)R and ET(B)R was determined by a reverse transcriptase polymerase chain reaction technique. PPET-1 and ET(A)R expression was up-regulated 4- and 3-fold, respectively, in both AA and CA diabetics (P<.05 vs non-diabetics). ET(B)R mRNA was significantly lower in AA diabetic patients. Function of ET-1 and ET receptors was assessed by vascular contractility assays. Vascular relaxation in response to sodium nitroprusside in arteries precontracted with ET-1 was significantly lower in AA (58% +/- 9) as compared to CA diabetics (74% +/- 5) (P<.05). In conclusion, this study demonstrated that the ET system is altered in favor of the contractile phenotype in AA diabetics and may contribute to the increased incidence of vascular complications in this population.
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PMID:Selective downregulation of endothelin-B receptors in diabetic African-American patients. 1191 20

Coronary arteries from animals on normal diets (ND) exhibit well-maintained responses to dilators under ischemic conditions. The reported altered metabolic requirements and K+-currents in blood vessels from hypercholesterolemic animals fed high-fat diets (HF) led us to hypothesize that under metabolically depressed conditions (N2/2-deoxyglucose) coronary arteries from pigs would exhibit significantly decreased responses to adenosine (ADO) as compared with pigs given ND. Diet had no major effect on responses of coronary rings to ET-1, nor on the sensitivity to ADO or 2-chloroadenosine (2-CAD) relaxation under metabolically supported conditions. During metabolic inhibition the response curves for both ADO and 2-CAD were shifted to the right (P < 0.05), with the HF group shifted about 4-fold more than ND (P < 0.05). To determine the involvement of K+-channels, ADO responses were measured in the presence of 4-aminopyridine (4-AP, 1 mM) or glybenclamide (GLYB, 10 microM). The larger shift in the HF group during metabolic inhibition was not affected by GLYB, but disappeared in the presence of 4-AP with ND now behaving similarly to HF. These results indicate that HF diet may have a 4-AP-like effect on voltage-dependent K+-channels (KV). Patch-clamp measures of whole cell K- currents showed the HF cells to have reduced 4-AP sensitive currents (P < 0.02). The 4-AP insensitive currents were similar in both groups. Thus, reduced KV channel activity may play a role in the depressed ADO relaxation associated with metabolic inhibition of HF coronary arteries. These factors may place the coronary circulation of HF at increased risk during an ischemic episode.
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PMID:High-fat diet alters K+-currents in porcine coronary arteries and adenosine sensitivity during metabolic inhibition. 1508 60

The aim of our research was to assess the role of vasoactive factors of endothelium (NO and endothelin-1) during diastolic dysfunction of the left ventricle and to determine the effects of nebivolol in the early treatment period of endothelial dysfunction. In the investigation were included 36 male patients (mean age 49+/-6 years) with LVDD due to CAD (22 patients) and essential hypertension (14 patients) as well as in 18 male patients (control group, 12 patients with CAD and 6 with hypertension) without LVDD of matched age, who underwent 2 week treatment with 5 mg nebivolol (Nebilet, Berlin-Chime) . The endothelial dysfunction was assessed by (a) a noninvasive method, brachial artery ultrasound during reactive hyperemia, measured by flow-mediated vasodilatation (FMD), which indirectly reflects the amount of NO and (b) measurement of the amount of ET-1 in the plasma by method of an enzyme-linked immunoassay (ELISA). According to the results of our studies FMD (%) was increased by 73% among the patients with DD of LV whereas among the patients without DD was increased by 66% (p<0,05). Furthermore, statistically none significant decrease of endothelin-1 levels were observed and no difference was found among the groups of patients. Importantly, statistically significant increase of early ventricular filling was found: E/A ratio with Doppler echocardiography at the end of 2 week period treatment reached 1,10+/-0,04 vs. 0,92+/-0,01 before the treatment (p<0,05). Positive correlation was found between FMD (%) and the relaxation capability of the left ventricle (r=0,38, p<0,05). Based on these results we can conclude that endothelial dysfunction might be indicator of LVDD, and by treating the former we can prevent the diastolic dysfunction.
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PMID:[Effects of nebivolol on endothelial dysfunction in patients with diastolic dysfunction of left ventricle]. 1678 65