Adrenal medullary storage vesicles of the spontaneously hypertensive rat

Abstract

The adrenal medullary vesicles of normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR) were examined in order to determine whether increased sympatho-adrenal activity plays a role in the elevation of blood pressure in the SHR. The uptake of 14C-epinephrine/100 μg of endogenous catecholamines in isolated SHR vesicles was higher than in NWR, while the uptake of 3H-metaraminol was the same as in NWR; thus, SHR vesicles exhibited a higher preference for epinephrine vs metaraminol compared to NWR. The difference in uptake was due to a lower K m for epinephrine in SHR. The storage of amines was the same in SHR and NWR, as demonstrated by measurements of catecholamine to ATP ratios in purified vesicles, and effluxes from the vesicles of endogenous and newly incorporated amines. The ratio of catecholamines to dopamine β-hydroxylase (DBH, a marker for storage vesicles) was higher in SHR for three reasons: (1) there were fewer vesicles per gland; (2) there was less DBH per vesicle, indicated by an increased precursor/product ratio; and (3) there was a higher catecholamine content per vesicle, as shown by an increase in the ratio of heavy to light vesicles on discontinuous sucrose density gradients. SHR adrenals were depleted of catecholamines after insulin administration to a greater extent than were NWR adrenals, and both SHR and NWR exhibited induction of tyrosine hydroxylase and dopamine β-hydroxylase after insulin. None of these findings is consistent with the view that sympathoadrenal hyperactivity occurs in the SHR; the data suggest that hypoactivity occurs, perhaps secondarily to the hypertension.