Biochemical and morphologic evaluation of the adrenal gland in the spontaneously hypertensive rat: Analysis of the segregating F2 population

The adrenal gland has been implicated in the hypertension of the spontaneously hypertensive rat (SHR). However, recent evidence suggests WKY rats are not as inbred as SHR and thus differences between the two strains may be strain related. In this study the segregating F2 populations of a SHR-WKY hybrid (F1) is used to assess changes in adrenal function during hypertension. Adrenal function was evaluated by analysis of steroidogenesis in adrenal homogenates incubated with progesterone and by measurement of catecholamine content in adrenals obtained by uniadrenalectomy under anesthesia at 6, 9, 12, and 17 weeks of age. In addition 24-hour urinary excretion of corticosterone and catecholamines was assessed. Quantitation was by HPLC. SHR were found to have increased norepinephrine compared to WKY with the most significant difference occurring in the prehypertensive period. The epinephrine was similar in the two strains at all ages. The ratio of norepinephrine to epinephrine was significantly greater in SHR than WKY, particularly in the prehypertensive ages. SHR also excreted more norepinephrine, but not epinephrine, over a 24 hour period than WKY. In F2 a significant correlation of norepinephrine with blood pressure was observed, with those F2 eventually developing hypertension having increased levels of this catecholamine. Epinephrine levels were not correlated with hypertension in F2. However the norepinephrine to epinephrine ratio did correlate with hypertension, as did the 24 hour excretion of norepinephrine. An increased conversion rate of progesterone to corticosterone without change in conversion rate to 18-OH DOC or DOC was observed in SHR compared to WKY but not in F2. A decrease in corticosterone excretion was also noted in prehypertensive SHR which gradually abated as hypertension developed. These findings were not observed in F2. We conclude that abnormal catecholamine content and relative proportions precede the elevation of blood pressure in both SHR and the F2. While the role of the adrenal cortex remains equivocal, these changes in the adrenal medulla may have a pathogenetic role in hypertension and could serve as effective biochemical markers for the development of the condition.