gms | German Medical Science

Potential mechanisms responsible for sympathetic activation occuring in essential hypertension include central mechanisms, alterations in norepinephrine disposition and interaction with other neurohumoral factors.

Regional sympathetic activation was studied comprehensively using microneurography and radiotracer dilution methodology in 24 untreated hypertensive patients and 11 age-matched normotensive subjects both before and after intravenous administration of the neuronal norepinephrine (NE) reuptake inhibitor desipramine (0.3mg/kg). Regional angiotensin II concentrations were measured in parallel. Compared to their normotensive counterparts, hypertensive subjects displayed increased muscle sympathetic nerve activity (p<0.01) and total systemic and regional (cardiac and renal) NE spillover at baseline (p<0.05). Whole body NE reuptake and the fractional extraction of 3[H]NE across the heart, an indicator of cardiac neuronal NE reuptake, were lower in hypertensive subjects (58±15vs70±12%; p<0.05). Desipramine lowered total body NE spillover by ~25-30% in both groups but elicited a more pronounced reduction of fractional 3[H]NE extraction in normotensive subjects than in hypertensive subjects (-51±12vs-37±10%;p<0.05). Cardiac NE spillover increased only in normotensive subjects and was similar to that of hypertensive subjects after desipramine infusion (23.5±12.9 vs 24.2±12.8ng/min;p=ns). DNA sequencing analysis of the NE transporter gene did not reveal any mutations which could account for reduced transporter activity. Arterial and coronary sinus angiotensin II concentrations did not differ between the two groups and were not related to indices of sympathetic activation.

Increased rates of sympathetic nerve firing and reduced neuronal reuptake of norepinephrine both contribute to sympathetic activation in essential hypertension, whereas a peripheral neuromodulating influence of angiotensin II seems to be excluded.