Glucocorticoid-induced hypertension in rats: role of the central muscarinic cholinergic system.
Betamethasone was administered on alternate days to rats, and the role of the central cholinergic system in the development of hypertension assessed. After 15 days of treatment the systolic blood pressure of treated rats was significantly higher than that of control rats. Peripheral administration of atropine but not of methyl atropine reduced systolic pressure in glucocorticoid-treated rats and had no effect in controls. Therefore, [3H]quinuclidinyl benzylate binding, sodium-dependent high-affinity choline uptake and choline acetyltransferase studies were performed in the septal area, anteroventrolateral medulla (AVLM), anterior hypothalamic preoptic area (AH/PO) and hypothalamus. The density of muscarinic receptors was increased in the hypothalamus and AVLM of treated rats without significant changes in affinity. Choline acetyltransferase activity significantly decreased in the AVLM and increased in the AH/PO. In addition, a decrease in the hypothalamus and an increase in the AH/PO of sodium-dependent high-affinity choline uptake was observed in glucocorticoid-treated rats. These results suggest the presence of an enhanced muscarinic cholinergic activity in several brain nuclei in rats with glucocorticoid-induced hypertension. This activation could be due to pre- and post-synaptic hypersensitivity.
Torres
N
N
Sección-Sustancias Vasoactivas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Fanelli
M
M
Alvarez
A L
AL
Santajuliana
D
D
Finkielman
S
S
Pirola
C J
CJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001623:Betamethasone / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*
D011976:Receptors, Muscarinic; D001285:Atropine; D001623:Betamethasone; D002794:Choline