Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of calcium channel antagonists, felodipine and cadmium, as well as pertussis toxin on noradrenaline-induced contractions in pulmonary artery rings from rats with pulmonary hypertension induced by monocrotaline (MCT) were examined. MCT-treated rats had pulmonary hypertension, right ventricular hypertrophy and lung oedema, as compared to corresponding vehicle-treated rats. The MCT-treated animals did not have polycythemia as compared to vehicle-treated rats. Pre-treatment of pulmonary artery rings from MCT-treated rats with felodipine and cadmium significantly reduced the maximum response without altering the EC50 or the Hill coefficient of concentration-response curve to noradrenaline. In pulmonary artery rings from vehicle-treated rats, felodipine significantly increased the EC50 and reduced the maximum response and the Hill coefficient of the concentration-response curve to noradrenaline. In contrast, cadmium did not alter these parameters in pulmonary artery rings from vehicle-treated rats. Pertussis toxin did not affect noradrenaline-induced contractions in pulmonary artery rings from vehicle- or MCT-treated rats. Felodipine, cadmium and pertussis toxin were ineffective in inhibiting noradrenaline-induced contractions in aortic rings from either vehicle- or MCT-treated rats. Our results can be interpreted to indicate that alteration to voltage operated, felodipine-sensitive, calcium channels as well as, cadmium-sensitive sites contribute to the changes observed in the functional behavior of pulmonary blood vessels from pulmonary hypertensive rats.
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PMID:Effects of calcium channel antagonists and pertussis toxin on noradrenaline-induced contractions in pulmonary artery from pulmonary hypertensive rats. 747 94

The effect of left ventricular hypertrophy (LVH) due to chronic pressure overload on right atrial (RA) and left ventricular (LV) myocardial beta-adrenergic receptor (beta-AR) density and subtypes, adenylyl cyclase (AC) activity and ADP-pertussis toxin ribosylated proteins was investigated in humans with LVH due to aortic stenosis and in patients without LVH undergoing heart surgery for mitral stenosis or coronary artery disease taken as controls. Both groups presented normal systolic function or plasma catecholamine levels. In LVH and controls, beta-AR density was similar in RA (62 +/- 6 vs 77 +/- 12 fmol.mg-1 protein) and LV (39 +/- 7 vs 32 +/- 2 fmol.mg-1 protein). In LVH, beta 1-AR percentage was < than in controls in LV (35 +/- 11 vs 73 +/- 5%, P < 0.05) but not in RA (79 +/- 5 vs 73 +/- 8%). Basal AC activity in RA (19 +/- 4 vs 21 +/- 6 pmol.mg-1 protein) and LV (22 +/- 5 vs 27 +/- 3 pmol.mg-1 protein) was similar in LVH and in controls. Isoprenaline-induced stimulation of AC in RA was similar in LVH and in controls (51 +/- 18 vs 36 +/- 18%) but < in LV of LVH (7 +/- 6 vs 45 +/- 6%, P < 0.05). In the presence of ICI-118,551 (a beta 2-adrenoceptor antagonist), isoprenaline failed to induce any increase in cAMP in LVH. The quantification of ADP-pertussis toxin ribosylated proteins indicated a lower concentration of substrates in LV myocardial membranes from LVH. These data indicate that in LVH due to pressure overload, there is a down-regulation of beta 1-AR and an increase in beta 2-AR density. This is associated with alterations of the transmembrane signalling marked by a decreased capacity of isoprenaline to stimulate AC and an impaired expression of Gi proteins.
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PMID:Cardiac beta-adrenoceptors and adenylyl cyclase activity in human left ventricular hypertrophy due to pressure overload. 818 1

1. Desensitization of the myocardial beta-adrenergic signal transduction pathway is an important mechanism which is involved in the progression of hypertensive heart disease. The aim of the present study was to evaluate the differential effects of chronic pharmacotherapy with an angiotensin converting enzyme (ACE)-inhibitor, an AT1-receptor antagonist and a direct vasodilator on blood pressure, cardiac hypertrophy and the beta-adrenergic signal transduction. Therefore, transgenic TG(mREN2)27 (TG) rats overexpressing the mouse renin gene were used. This strain is characterized by the development of fulminant hypertension with cardiac hypertrophy. 2. Seven week old heterozygous TG(mREN2)27 rats were treated for 11 weeks with the AT1-receptor antagonist losartan (10 mg kg[-1]), the ACE-inhibitor quinapril (15 mg kg[-1]) and the direct vasodilator hydralazine (30 mg kg[-1]). Untreated TG and normotensive Sprague-Dawley rats (SD) served as controls. 3. TG(mREN2)27-rats were characterized by arterial hypertension (TG 194+/-3.2 mmHg vs SD 136+/-2.9 mmHg systolic blood pressure), increased left ventricular weights (TG 4.3+/-0.3 vs SD 3.0+/-0.1 mg g(-1) body weight), decreased myocardial neuropeptide Y (NPY) concentrations (TG 1143+/-108 vs SD 1953+/-134 pg g(-1) wet weight), reduced beta-adrenoceptor densities (TG 51.1+/-1.9 vs SD 63.4+/-3.7 fmol mg[-1]) as assessed by [125I]-cyanopindolol binding studies, and increased Gi(alpha)-activities (TG 4151+/-181 vs SD 3169+/-130 densitometric units) as assessed by pertussis toxin catalyzed [32P]-ADP-ribosylation. Downregulation of beta-adrenoceptors and increased Gi(alpha) were accompanied by significantly reduced isoprenaline-, Gpp(NH)p- and forskolin-stimulated adenylyl cyclase activity. Catalyst activity as determined by forskolin plus Mn2+ co-stimulation of adenylyl cyclase did not differ between TG(mREN2)27- and SD control-rats. 4. Losartan and quinapril significantly restored systolic blood pressures, left ventricular weights, beta-adrenoceptor densities, myocardial neuropeptide Y-concentrations, adenylyl cyclase activities and Gi(alpha)-activities towards the values in Sprague-Dawley-controls. No differences were observed between the effects of quinapril- and losartan-treatment. In contrast, hydralazine had only minor effects on blood pressure reduction, regression of left ventricular hypertrophy and neuroeffector defects in TG(mREN2)27. 5. In conclusion, direct vasodilatation is not able to overcome the pathophysiological alterations in TG caused by transgene overexpression. In contrast, ACE-inhibitors and AT1-receptor antagonists, which inhibit the renin angiotensin system, equally exert beneficial effects on blood pressure, myocardial hypertrophy and neuroeffector mechanisms. Modulation of the sympathetic tone and resensitization of the beta-adrenergic signal transduction system may contribute to the special effectiveness of these drugs in the treatment of the hypertensive cardiomyopathy.
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PMID:Effects of quinapril, losartan and hydralazine on cardiac hypertrophy and beta-adrenergic neuroeffector mechanisms in transgenic (mREN2)27 rats. 950 80