Central role for vasopressin in cardiovascular regulation and the pathogenesis of hypertension.

Abstract

In recent years the role of neuropeptides in the central regulation of arterial pressure and the pathogenesis of hypertension has been the subject of considerable attention. Of all the neuropeptides, vasopressin (AVP) has been one of the most widely studied. The availability of sophisticated immunocytochemical and biochemical methods has permitted localization of AVP in areas of the brain known to be involved in cardiovascular regulation. In addition, specific AVP receptors with high affinity have been found in these brain areas.Several lines of evidence suggest that central AVP plays a role in the control of blood pressure and heart rate in both normotensive and hypertensive animals. Administration of AVP into the central nervous system produces changes in arterial pressure and heart rate that can be reversed by competitive antagonists. AVP interacts with neurotransmitters such as catecholamines, which are involved in arterial pressure regulation. It is also a potent releasing factor for adrenocorticotropic hormone (ACTH)-corticosterone, which in turn acts on the cardiovascular system. Agents that inhibit the interaction of AVP with its receptors have cardiovascular effects. Furthermore, levels of AVP and its receptor are altered in hypertensive states. Finally, increased sensitivity to the pressor effects of AVP has been described in experimental models of hypertension.This review will focus on evidence for a central role for AVP in cardiovascular regulation and the pathogenesis of hypertension, and discussion will mainly focus on work done in rats. It should be noted that there is increasing evidence for species differences in responsiveness to AVP and mechanisms of action of AVP. For a more detailed discussion of the neuroanatomy, biochemistry, molecular biology, and physiology of this peptide,

Effect of vasopressin antagonism on renal handling of sodium and water and central and brachial blood pressure during inhibition of the nitric oxide system in healthy subjects

“…However, pulse rate values were approximately 2 beats per minute lower in the tolvaptan group compared to the placebo group. Most likely, this slight decrease in pulse rate is due to increased baroreceptor sensitivity exerted by AVP [36,37]. However this had no net effect on BP.…”

OPC-21268, a vasopressin V1 antagonist, produces hypotension in spontaneously hypertensive rats.

“…Reports conflict concerning the central role of AVP in genetic hypertension, 29 but hypotensive effects of centrally administered AVP in SHRSP 30 and lower hypothalamic AVP contents in SHR 27 were reported, and these findings suggest that AVP acts centrally to depress cardiovascular activities and that low concentrations of AVP in hypothalamic nuclei contribute to hypertension in SHR or SHRSP. Therefore, if OPC-21268 antagonizes to AVP in the central nervous system, the blood pressure should be further elevated.…”

Angiotensin II type 2 receptors have a major somatodendritic distribution in vasopressin-containing neurons in the mouse hypothalamic paraventricular nucleus

“…Release of VP from the posterior pituitary into the general circulation maintains body fluid balance by stimulating water reabsorption by the kidney (Bourque, 1998). In the NTS and spinal cord, VP is involved in regulating the baroreflex and sympathetic outflow (Gardiner and Bennett, 1986; Berecek and Swords, 1990; Toba et al, 1998; Raggenbass, 2001). Although the PVN subdivisions are less clearly defined in the mouse (Van Pett et al, 2000), the present ultrastructural findings indicate that AT2 receptors have a specific subcellular distribution in the PVN that is permitting for functional participation in the regulation of neuroendocrine and cardiovascular homeostatic functions.…”