Human adrenoceptor system response to the development of high altitude pulmonary arterial hypertension.
High-altitude pulmonary arterial hypertension affects people with a long-term residence at altitudes over 2500 m above the sea level and is characterized by elevated pulmonary artery pressure (over 35/15 mmHg). In order to assess the role of beta-adrenoreceptors in the development of high-altitude pulmonary arterial hypertension, we studied the beta-adrenoreceptor density on mononuclear leukocytes in Kirghiz male natives of Eastern Pamir (3600-4200 m above sea level) with the diagnosis of high-altitude pulmonary arterial hypertension, and in healthy men. It was shown that patients with signs of right ventricular hypertrophy (RVH) of the second and third grade have beta-adrenoreceptor density 4.5 times lower than control (2.27 +/- 0.22 vs. 9.85 +/- 1.28 fmol/10(6) cells). Values of Kd also proved to be lower, by 2.5 times (0.57 +/- 0.14 vs. 1.44 +/- 0.18 nM). Stimulation of adenylate cyclase by isoproterenol and other beta-agonists was lower in patients than in controls (+33% and +120%, respectively). These results demonstrate that the desensitization of beta-adrenoreceptors is present in patients with high-altitude pulmonary arterial hypertension associated with severe right ventricular hypertrophy. Patients with pulmonary arterial hypertension due to mitral stenosis do not have any signs of beta-adrenoreceptor desensitization associated with high plasma levels of catecholamines.
Aldashev
A A
AA
Kirghiz Institute of Cardiology, USSR.
Borbugulov
U M
UM
Davletov
B A
BA
Mirrakhimov
M M
MM
D000262:Adenylyl Cyclases / Q000097:blood; D000328:Adult; D000531:Altitude / Q000009:adverse effects*; D000818:Animals; D006332:Cardiomegaly / Q000097:blood / Q000209:etiology; D000242:Cyclic AMP / Q000097:blood; D004082:Dihydroalprenolol / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000209:etiology*; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D004082:Dihydroalprenolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases