[Primary pulmonary hypertension: activation of sympathico-adrenal system and free radical oxidation. Positive effects of carvedilol therapy].
OBJECTIVE
To study the condition of the sympathico-adrenal system (SAS), synthesis of cAMP dependent on beta2-adrenoreceptors and parameters of free radical oxidation in patients with primary pulmonary hypertension (PPH); to examine efficacy of non-selective beta- and alpha1-adrenoblocker carvedilol in PPH patients.


METHODS
Twenty patients with PPH had 6-minute walk test, ECG monitoring with assessment of heart rhythm variability (HRV). Tests for noradrenalin and adrenalin concentration in blood plasma, cAMP synthesis by blood lymphocytes in basal conditions and under stimulation with isoproterenol and forskolin, free radical oxidation were made initially, 1 and 6 months later. Ten patients received carvedilol in addition to standard therapy, 10 patients served control.


RESULTS
PPH patients had higher NA in the blood, low cAMP synthesis, high malonic aldehyde, low activity of glutathionperoxidase, increased activity of superoxidedismutase and catalase of erythrocytes. The most pronounced changes in the above parameters were observed in patients with PPH FC III-IV. HRV declined in progression of cardiac failure. 6-months of combined treatment with carvedilol increased the distance of 6-min walk. Carvedilol had no effect on HRV, it reduced NA, stimulated cAMP synthesis, demonstrated no antioxidant activity.


CONCLUSIONS
In PPH there is activation of SAS and desensitization of beta2-AR cells, oxidative stress develops. Addition of carvedilol to standard therapy with PPH improves clinical condition due to adrenoblocking properties of the drug.
Chazova
I E
IE
Irodova
N L
NL
Krasnikova
T L
TL
Aref'eva
T I
TI
Lazutkina
V K
VK
Orlova
Ia A
IaA
Sokolov
S F
SF
Ataullakhanova
D M
DM
Masenko
V P
VP
Konovalova
G G
GG
Lankin
V Z
VZ
D018663:Adrenergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D002374:Catalase / Q000097:blood; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D013564:Sympathetic Nervous System / Q000187:drug effects*
D018663:Adrenergic Agents; D000959:Antihypertensive Agents; D002227:Carbazoles; D005609:Free Radicals; D011412:Propanolamines; D000077261:Carvedilol; D008315:Malondialdehyde; D010088:Oxidoreductases; C121849:superoxide reductase; D002374:Catalase