CENTRAL VASOPRESSIN IN EXPERIMENTAL AORTIC-STENOSIS IN THE RAT

Objective: In several forms of heart disease characterised by low card iac output, activated neurohumoral systems including increased vasopre ssin plasma levels play a key role in the changes in cardiovascular fu nction. The aim of this study was to test the hypothesis that under su ch conditions the central vasopressin system might also be altered, wh ich could contribute to deranged cardiovascular control. Methods: Aort ic stenosis was produced in 22 rats by placing a Silver clip (inner di ameter 0.6 mm) on the ascending aorta. After 12 weeks, haemodynamic an d hormonal measurements were performed, and vasopressin content was de termined in 20 microdissected brain areas (micropunch technique). Twen ty two sham operated rats served as controls. Results: Twelve weeks af ter placing the supravalvular clip, significant aortic stenosis was do cumented by left ventricular myocardial hypertrophy. Cardiac index was significantly reduced and the peripheral vascular resistance index wa s increased, while poststenotic aortic pressure was non-significantly decreased. Plasma renin concentration [6.8(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 nor adrenaline remained unaltered. The vasopressin content was significant ly altered in eight out of 20 brain areas investigated. Concerning the vasopressin producing hypothalamic nuclei, concentrations were increa sed 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 sh owed significantly raised vasopressin concentrations in the median emi nence [25 186(1682) v 37 367(1345) pg.mg(-1) protein, P< 0.01], where the hormone is mainly concentrated in the hypothalamo-hypophysial trac t. Vasopressin content was significantly decreased in locus coeruleus [49(5) v 89(6) pg.mg(-1) protein], which is known to be involved in mo dulation of sympathetic activity. Conclusions: As well as showing incr eased secretion of vasopressin into the blood with consecutive periphe ral antidiuretic and vasoconstrictive effects, these data suggest an a lteration in the central vasopressin system in aortic stenosis which m ight transmit cardiovascular effects by neuromodulation and neuroregul ation.