Responses of rabbit basilar arteries to vasoconstrictor and vasodilator agents: The effects of atherosclerosis, age and sex

We have studied the influences of atherosclerosis, age and sex on arterial responsiveness to vasoactive agents using male and female Watanabe heritable hyperlipidaemic (WHHL) rabbits (4-12 months, n = 36) as a model for athcrosclcrosis and sex- and agc-matchcd New Zealand White (NZW) rabbits (n = 36) as controls. The responses of isolated rings of basilar arteries mounted in organ baths to vasoactive substances were studied. KCl-induced contractions in female atherosclerotic rabbits were greater than controls but those of male atherosclerotic rabbits were equivalent to the respective controls. Age did not influence KCl-induced contractions of rabbits of either strain or sex. Histamine-induced contractions increased with age in female atherosclerotic rabbits only. Acetylcholine (ACh)-induced relaxations of 6-month-old male and female atherosclerotic rabbits were greater than their respective controls. ACh-induced relaxations of female but not male NZW rabbits decreased with age. Calcitonin gene-related peptide- and vasoactive intestinal polypeptide- induced relaxations in atherosclerotic male and female rabbits were not affected by age. However, relaxations of female but not male control rabbits decreased with age. These findings suggest that there are subtle changes in the control of vascular tone which develop with the onset and progression of atherosclerosis. Of particular significance is the increase in endothelium-dependent relaxation in WHHL rabbits. Sexual dimorphism in vascular reactivity is also indicated by (1) the increase in contractility in female but not male WHHL rabbits and (2) the age-dependent decrease in endothelium-dependent and endothelium-independent relaxation in female but not male control (NZW) rabbits that is coincident with the onset of sexual maturity.