Central vasopressin in experimental aortic stenosis in the rat

Objective: In several forms of heart disease characterised by low cardiac output, activated neurohumoral systems including increased vasopressin plasma levels play a key role in the changes in cardiovascular function. The aim of this study was to test the hypothesis that under such conditions the central vasopressin system might also be altered, which could contribute to deranged cardiovascular control. Methods: Aortic stenosis was produced in 22 rats by placing a Silver clip (inner diameter 0.6 mm) on the ascending aorta. After 12 weeks, haemodynamic and hormonal measurements were performed, and vasopressin content was determined in 20 microdissected brain areas (micropunch technique). Twenty two sham operated rats served as controls. Results: Twelve weeks after placing the supravalvular clip, significant aortic stenosis was documented by left ventricular myocardial hypertrophy. Cardiac index was significantly reduced and the peripheral vascular resistance index was increased, while poststenotic aortic pressure was non-significantly decreased. Plasma renin concentration 16.8(SEM 0.9) v 2.1(0.2) ngAI·ml^-1·h^-1 in controls] and plasma vasopressin [32.9(12.5) v 18.4(6.0) pg·ml^-1] were significantly increased, while plasma and urinary noradrenaline remained unaltered. The vasopressin content was significantly altered in eight out of 20 brain areas investigated. Concerning the vasopressin producing hypothalamic nuclei, concentrations were increased in the paraventricular [7494(360) v 4744(237) pg·mg^-1 protein, P < 0.05] and suprachiasmatic [3613(170) v 1784(197) pg·mg^-1 protein, P < 0.01], but not in the supraoptic nuclei. Rats with aortic stenosis showed significantly raised vasopressin concentrations in the median eminence [25 186(1682) v 37 367(1345) pg·mg^-1 protein, P < 0.01], where the hormone is mainly concentrated in the hypothalamo-hypophysial tract. Vasopressin content was significantly decreased in locus coeruleus [49(5) v 89(6) pg·mg^-1 protein], which is known to be involved in modulation of sympathetic activity. Conclusions: As well as showing increased secretion of vasopressin into the blood with consecutive peripheral antidiuretic and vasoconstrictive effects, these data suggest an alteration in the central vasopressin system in aortic stenosis which might transmit cardiovascular effects by neuromodulation and neuroregulation.