Opioids exert depressor effects on cardiovascular responses through sympathetic nervous system inhibition. Research suggests that opioid inhibition of sympathetic activity may be compromised in hypertension. Preliminary studies by the Principal Investigator suggest that the nature of this compromise may be influenced by age and race. Additionally, literature suggests that hypertension chronicity may modulate opioid sympathoinhibitory actions. The receptor mechanisms mediating the observed modulating effects of age, race, and hypertension chronicity on opioidergic inhibition and regulation of blood pressure remain to be determined. The goals of the proposed studies, therefore, are to: (a) confirm the preliminary findings of age, race, and hypertension chronicity effects on opioid and cardiovascular responses to stress, (b) determine the opioid mechanisms mediating these effects using an opioid receptor blockade strategy. To achieve these goals, two double-blind, placebo-controlled cross-over studies are proposed in which we will evaluate the effects of naltrexone hydrochloride, an oral opiate antagonist, on adrenergically-mediated cardiovascular responses in older and younger, Black and White normotensives and hypertensives with varying lengths of hypertension duration. Cardiovascular and opioid responses will be measured in response to a stressor combined with either placebo or naltrexone pretreatment. Results from these studies will assist in (a) elucidating opioidergic mechanisms underlying the increased rates of hypertension morbidity and mortality among Blacks and the elderly, and (b) ultimately optimizing the design of pharmacological interventions for the prevention and treatment of hypertension.
| Svetkey, L P; Timmons, P Z; Emovon, O et al. (1996) Association of hypertension with beta2- and alpha2c10-adrenergic receptor genotype. Hypertension 27:1210-5 |
