Blood pressure and heart rate response to central beta-blockade in conscious rats with glucocorticoid-induced hypertension.
The beta-adrenergic antagonist propranolol, administered subcutaneously to conscious adrenalectomized rats made hypertensive by exogenous glucocorticoids, has been shown to induce acutely a marked fall in blood pressure and heart rate. These animals almost completely lacked circulating epinephrine. Because both changes were closely related, it was suggested that in this model of hypertension propranolol acts via a central mechanism. To test this hypothesis, we now administered sotalol (300 micrograms) intracerebroventricularly to unanesthetized adrenalectomized rats with glucocorticoid-induced hypertension (this hydrophilic beta-blocking agent does not cross the blood-brain barrier). The same experiments were also performed in sham-operated glucocorticoid-hypertensive rats. On the day of the study, there was no significant difference between adrenalectomized and sham-operated groups of rats in intraarterial pressure and heart rate. Sotalol increased blood pressure and significantly slowed heart rate during the 60-min observation period, both in adrenalectomized and sham-operated rats. Sotalol's vehicle had no blood pressure effect and caused a transient heart rate acceleration in rats with, as well as without, circulating epinephrine. These results therefore suggest that the previously observed enhanced effect of peripherally administered propranolol in the absence of detectable circulating epinephrine, in this model, is not mediated centrally.
Burris
J
J
Waeber
B
B
Nussberger
J
J
Brunner
H R
HR
D000315:Adrenalectomy; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D005938:Glucocorticoids; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013015:Sotalol / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D005938:Glucocorticoids; D013015:Sotalol