Re-expression of alpha skeletal actin and regulation of alpha 1 adrenoceptor signalling in DOCA-salt hypertension in rats.
OBJECTIVE
To determine the effects of increased sympathetic nervous system activity in humoral hypertension on the regulation of surface alpha 1 adrenoceptors and signal transduction, deoxycorticosterone acetate (DOCA) salt hypertension was induced in rats and the animals killed three weeks following the initiation of hypertension.


METHODS
Experiments were performed on male Sprague-Dawley rats, weighing 250-300 g, divided into two groups: DOCA-salt (n = 75), and control (n = 60). Radioligand binding studies of the alpha 1 adrenoceptors, noradrenaline stimulated phosphoinositol turnover, ADP ribosylation of 41 kD substrate by pertussis toxin, and myocardial noradrenaline content were measured in the ventricular myocardium. The expression of sarcomeric actin isoforms was examined by northern blot and hybridisation with specific oligonucleotide probes.


RESULTS
The density of alpha 1 adrenoceptors was decreased by 51% in DOCA-salt treated rats. However, noradrenaline stimulated phosphoinositol turnover in myocytes from DOCA-salt hearts was not diminished. The relative quantities of pertussis toxin labelled substrates did not differ in experimental and control hearts. Myocardial noradrenaline content was reduced by 60% in DOCA-salt hearts. Northern blots on RNA extracted from hypertrophic hearts of DOCA-salt treated rats showed an upregulation of alpha skeletal actin.


CONCLUSIONS
The adrenergic state present in short term DOCA-salt hypertensive hypertrophy is characterised by enhanced signal transduction via the alpha 1 adrenoceptors and the re-expression of alpha skeletal actin in enlarging myocytes.
Meggs
L G
LG
Department of Medicine, New York Medical College, Valhalla 10595.
Huang
H
H
Tillotson
J
J
Capasso
J M
JM
Anversa
P
P
D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D015152:Blotting, Northern; D003900:Desoxycorticosterone; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D000199:Actins; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D003900:Desoxycorticosterone; D009638:Norepinephrine