gms | German Medical Science

Background: Essential hypertension is commonly associated with sympathetic activation. The precise causal mechanisms leading to sympathetic activation in hypertensive subjects are still poorly understood. Amongst others, possible explanations include sympathetic hyperinnervation of target tissues, as evident in the spontaneously hypertensive rat.

Methods: To further address this issue we combined biochemical measurements of cardiac NE stores (n=112), measured from the rate of overflow of the NE metabolite, dihydroxyphenylglycol (DHPG), and its tritiated form into the coronary sinus during an infusion of [3H]NE), with 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy (n=16) as indices of cardiac sympathetic innervation in normotensive (NT: n=73/8) and hypertensive (EH: n=39/8) subjects. To complement these data, we also determined the transcardiac gradients for plasma nerve growth factor (NGF) (ELISA), a neurotrophin produced and released by target tissues which plays a pivotal role in the differentiation, maturation and survival of sympathetic neurons.

Results: Cardiac NE stores were substantially reduced in hypertensive subjects (NT: 713plusminus67 vs EH: 328plusminus180 nmol; p<0.05). The heart-to-mediastinum (H/M) uptake ratio of MIBG was significantly lower in the hypertensive group (NT: 2.31plusminus0.12 vs EH: 1.98plusminus0.20; p<0.01). Furthermore, the plasma NGF gradient across the heart was reduced in hypertensive patients (NT: 21.1plusminus6.6 vs EH: -5.8plusminus6.2pg/ml; p<0.05).

Conclusions: In contrast to animal models of hypertension, these data provide biochemical, scintigraphic and biological evidence for reduced myocardial sympathetic innervation in human essential hypertension.