Hypotensive effects of cardiac glycosides in spontaneously hypertensive rats
Ayachi, S.; Brown, A.M.
Journal of Pharmacology and Experimental Therapeutics 213(3): 520-524
1980
ISSN/ISBN: 0022-3565 PMID: 7205616 Document Number: 166832
The effects of cardiac glycosides on systolic arterial pressure (SAP) and heart rate (HR) were studied in spontaneously hypertensive (SH) and normotensive (NT) Wistar rats. Ouabain (2 mg/kg), given by i.p. injection to unanesthetized rats, produced a significant decrease in SAP in both SH and NT rats with little concomitant HR change. Baroreceptor denervation abolished the response. To analyze the effects more completely, experiments were done on acutely anesthetized rats. Ouabain was administered i.p. 30 min after induction of anesthesia with alpha-chloralose (60 mg/kg i.p.). alpha-Chloralose alone produced a significant SAP decrease in both SH and NT rats and bradycardia in SH but no significant HR change in NT rats. Ouabain i.p. further reduced SAP in SH but had no effect on NT rats. When given by i.a. bolus injection (250 microgram in 0.1 mg of heparin-saline) to anesthetized (pentobarbital, 40 mg/kg i.p.) rats with intact left carotid sinus nerves, ouabain produced a transient but significant reduction in SAP of SH but NT rats or SH rats with sinoaortic denervation. Digitoxin, given by stomach tube (4--5 mg/kg) for 1 week, decreased SAP in SH but not NT rats. Digitoxin produced significant SAP increases in SH rats with sinoaortic denervation. Arterial baroreceptor discharge is increased by cardiac glycosides. The present results suggest that the reflex hypotensive effects of digitalis drugs are due, at least in part, to sensitization of baroreceptors and that SH rats may be more sensitive to these drugs possibly because of altered intrinsic baroreceptor properties.