Cardiovascular and sympathetic responses to chronic arachidonate in SHR and WKY rats.

Abstract

In rats between the ages of 4 and 12 or 14 weeks, repeated daily subcutaneous administration of arachidonate (AA) at a dose of 50 or 200 mg/kg significantly retarded the development of hypertension in spontaneously hypertensive rats (SHR) but did not alter the normal age-related increase in blood pressures (BP) of normotensive (WKY) rats. Heart rates (HR) and plasma levels of norepinephrine (NE), but not epinephrine, were lower in AA-treated SHR than in saline-treated animals. AA-treated SHR and WKY gained less weight than the saline-treated controls. In pithed AA-treated SHR, stimulation of the sympathetic outflow (50 V, for 1 minute at 0.3 or 3.0 Hz) and intravenous administration of NE (0.3 or 3.0 g/kg) evoked smaller pressor responses than in saline-treated controls, but the stimulation-evoked increases in plasma catecholamines were unchanged by AA treatment. These results indicated that, in SHR, chronic AA treatment reduces BP by mechanisms that do not directly affect NE release from sympathetic nerves. There appears to be both reduced central nervous system activation of the sympathetic outflow and diminished responses to peripheral sympathetic stimulation and exogeneous NE which may be secondary to the reduced vascular hypertrophy that usually accompanies the development of high BP in SHR.