Sympathetic and platelet adrenergic activity and salt sensitivity: an experimental study.

The objective of the study was to evaluate the advanced hypothesis that genetically predisposed salt-sensitivity contributes to an increased adrenergic susceptibility and platelet activity and both these factors play a role in the pathogenesis of hypertension in a Dahl rat model. The results showed: i) Dahl salt-sensitive rats (DS) gradually develop a diastolic hypertension by the end of 3 months of age, in spite of the diet they are fed. Low-Na diet (0.5% NaCl) does not prevent hypertension but delays its development. High-Na diet (8%) exacerbates their hypertension. ii) After 2 months of Na-loading, DS rats expressed significantly increased sodium and water retention and increased plasma volume by 15%, compared with 2.8% in Dahl salt-resistant (DR) rats on high-Na diet. iii) The increased activity of the sympathetic nervous system (SNS) in DS rats paralleled the development of hypertension and was stimulated by Na-loading. It was assessed by their catecholamines status and heart rate changes. iv) Platelet activity of DS rats was increased as reflected in collagen-induced nonstimulated and adrenaline-stimulated aggregation, and an increased plasma T x B2/6-keto PGF1 alpha ratio. Na-loading further increased platelet activity. v) Both DR and DS rat platelets displayed alpha 2-adrenoceptors (A2) of low binding capacity (Bmax 25 and 35 fmol/mg protein, respectively) and low affinity (KD 5.6 nM for both groups), suggesting that platelet alpha 2 adrenoceptors in this strain of rats might not play a significant biological role in their increased platelet activity. The fact that platelet alpha 2-adrenoceptors do not define the stimulation of SNS in DS rat do not exclude their participation in development of salt-dependent hypertension, since a genetic defect(s) of these ubiquitous receptors (brain, kidney, blood vessels) could still contribute to the pathogenesis of the disease.