Abnormal Storage of Norepinephrine in Experimental Hypertension in the Rat

Abstract

The storage and release of ³H-norepinephrine in the hearts of rats made hypertensive by desoxycorticosterone and NaCl is reported. The initial uptake of the labeled catecholamine was similar in hypertensive and normotensive groups. After an intravenous injection of ³H-norepinephrine, there was a greater and more prolonged fall in specific activity of cardiac norepineph-rine in the first few hours in the hypertensive animals. Subcellular distribution studies showed that in the hearts from hypertensive rats a greater proportion of the labeled amine was present in the soluble-cytoplasmic fraction than in the granular-storage fraction. In control rats an equilibrium between soluble and granular fractions was reached by 1 hr, while in the hypertensives it was not achieved within 24 hr. In the first few hours there was a 45% fall in specific activity in the granular fraction of the hypertensive rats, but only a small re-deuction in the controls. There was an elevation in the fraction of deaminated metabolites in the hearts of the hypertensive animals, while in the kidneys all ³H-metabolites were increased. These observations are consistent with the concept that there is a defect in the storage and retention of norepinephrine by granules in sympathetic nerves in this type of experimental hypertension. Such an abnormality might permit increased amounts of physiologically active cate-cholamine to be available to the receptor.