These studies are designed to investigate the contributions and interaction of two vasopressor systems i.e. vasopressin and the sympathetic nervous system in the maintenance of hypertension in the elderly (the thrid major pressor system, renin-angiotensin, having been shown to be suppressed in the elderly). In previous experimental studies we have found evidence suggesting that sodium may prompte high blood pressure by altering the characteristics of alpha2-adrenoceptors, and that the pressor effectiveness of vasopressin is greatly enhanced when the sympathetic system is impaired. In the present proposal we plan to establish the hormonal and alpha2-adrenoceptor profiles (from platelets) in young and old hypertensive and normotensive subjects, to separate alterations associated with hypertension from those attributable to normal aging. We also plan to conduct in elderly hypertensives inpatient metabolic studies to determine the possible pressor contributions of vasopressin (as assessed by blood pressure responses to a V1 inhibitor) after salt loading or sympathetic inhibiton (by clonidine or prazosin) and to test the effect of salt-loading on alpha2-adrenoceptors of salt-sensitive and salt-resistant hypertensives. Finally, we propose to test the therapeutic effect of a vasopressin inhibitor with combined V1 and V2 action in elderly hypertensives with diuretic-induced hyponatremia. These studies should advance our understanding of the mechanisms participating in the maintenance of the non-renin-dependent hypertension in the elderly. They may also provide information leading to new therapeutic approaches suitable for this type of hypertension as well as for the prevention or reversal of certain diuretic-induced complications.
| Bursztyn, M; Bresnahan, M; Gavras, I et al. (1990) Effect of aging on vasopressin, catecholamines, and alpha 2-adrenergic receptors. J Am Geriatr Soc 38:628-32 |
| Bursztyn, M; Bresnahan, M; Gavras, I et al. (1990) Pressor hormones in elderly hypertensive persons. Racial differences. Hypertension 15:I88-92 |
| Gavras, H; Gavras, I (1989) Salt-induced hypertension: the interactive role of vasopressin and of the sympathetic nervous system. J Hypertens 7:601-6 |
