Effects of chronic administration of atenolol on the in situ perfused mesentery of normotensive and hypertensive rats.
1. Atenolol 50 mg kg-1 was administered daily for 7 to 21 days to male normotensive Wistar rats and to Okamoto spontaneously hypertensive rats. Blood pressure and heart rate were monitored daily. 2. Following atenolol treatment the response to exogenous noradrenaline and to periarterial nerve stimulation was measured in the in situ blood perfused mesentery. 3. In normotensive animals, treatment with atenolol for 7 days had little effect on the responses of the mesenteric vasculature to either exogenous noradrenaline or to periarterial nerve stimulation. After 21 days, the response to noradrenaline was little changed, but there was a statistically significant decrease in the response to periarterial nerve stimulation at the higher stimulation frequencies (16 and 35 Hz). 4. In spontaneously hypertensive animals, treatment with atenolol for 7 days did not significantly affect the response of the mesenteric vasculature to either noradrenaline or periarterial nerve stimulation; however, after treatment for 21 days, responses to exogenous noradrenaline were reduced, while responses to periarterial nerve stimulation were even more markedly reduced, particularly at the lower stimulus frequencies. 5. The time course of the observed effects suggests that, over time, atenolol induces changes other than the simple blockade of beta-adrenoceptors which can be demonstrated to be present immediately. The decreased responses to periarterial nerve stimulation in normotensive and hypertensive animals suggest that the changes induced affect presynaptic mechanisms of noradrenaline release (either directly or indirectly), rather than changes in postsynaptic receptor sensitivity or vascular reactivity. The observation that the changes are more evident in hypertensive animals indicates that they may play an important role in the antihypertensive action of atenolol.
Draper
A J
AJ
School of Pharmacy and Pharmacology, University of Bath, UK.
Kingsbury
M P
MP
Redfern
P H
PH
Todd
M H
MH
D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*
D001262:Atenolol; D009638:Norepinephrine