Role of vasopressin in cardiovascular homeostasis and hypertension

Vasopressin has two major biological actions, vasoconstriction and antidiuresis, that are important variables in the control of blood pressure. However, the concentrations of vasopressin required for antidiuresis are 10-100 times less than those required to elevate the blood pressure in the intact organism. Vasoconstrictor potency of vasopressin in vitro, however, is of the same magnitude as the antidiuretic potency. This suggests that in the closed loop system in vivo vasopressin's pressor action is largely buffered by other cardiovascular homeostatic mechanisms. It has been clearly demonstrated that one such damping mechanisms is the sympathetic nervous system, and there is evidence that there is a quantitative interplay between vasopressin and angiotensin, such that the sum of their combined pressor effects is constant. There is increasing evidence that the vasoconstrictor action of vasopressin may play a role in the integrated cardiovascular response to orthostasis and volume depletion. Vasopressin is also of great importance in the response to haemorrhage and is essential for the compensatory rise in blood pressure after blood loss. Most studies agree that plasma vasopressin levels are elevated in experimental and human hypertension. Vasopressin has been postulated to be involved in the pathogenesis of hypertension. It could be involved by one of three mechanisms: as a direct vasoconstrictor, by its antidiuretic activity and hence by maintaining blood and extracellular volume, or by modulating and enhancing other vasopressor mechanisms. If it is to act as a direct vasoconstrictor some mechanisms of sensitization to the pressor effect of vasopressin need to be postulated. As yet there is very little evidence on this point. Furthermore, one needs to ask why in hypertension is there sensitization, whereas patients with high plasma vasopressin levels from SIADH do not develop sensitivity and are normotensive? Studies with the Brattleboro rat with genetic hypothalamic diabetes insipidus, as well as with the new specific competitive antagonists to the pressor actions of vasopressin, appear to rule out a direct vasoconstrictor role for vasopressin in experimental hypertension. Its role in the pathogenesis of essential hypertension is still undecided.