Vascular reactivity, tissue levels, and binding sites for endothelin: a comparison in the spontaneously hypertensive and Wistar–Kyoto rats

Abstract

The role of endothelin (ET-1) in mediating the development of blood pressure was investigated in the spontaneously hypertensive (SHR) rat using the Wistar–Kyoto (WKY) rat as the normotensive control. The following were characterized in both rat strains: age-dependent changes in mean arterial blood pressure (MAP), tissue (blood, lung, heart, and kidney) levels of immunoreactive ET-1 like related peptides (ET-1RP), aortic ring responses to ET-1, and specific high-affinity tissue (lung, atrium, ventricle, aorta, and kidney) binding sites for 125I-labelled ET-1. Commencing at age 10 weeks through to 12 weeks, SHR rats but not WKY rats developed a significant increase in MAP (from 152 ± 7 to 189 ± 3 mmHg) (1 mmHg = 133.32 Pa). However, in both WKY and SHR rats immunoreactive levels of ET-1RP increased (100 and 80%, respectively) throughout the same measurement period. The potency of ET-1 to contract aortic rings from SHR rats was slightly but not significantly greater than that for aortic rings from WKY rats, although aortic rings from SHR rats contracted in the presence of 0.5 nM ET-1, while those from WKY rats did not. The levels of immunoreactive ET-1RP were significantly reduced (32%) in the kidney and unchanged in the heart and lung of SHR rats compared with WKY rats. Specific 125I-labelled ET-1 binding sites displayed an increase and a significant decrease (24%) of density in the atrium and ventricle, respectively, a significant increase (31%) of affinity in the lung, and were unchanged in the kidney and aorta of SHR rats compared with WKY rats following the development of hypertension. The lack of a correlation between circulating levels of immunoreactive ET-1RP and the development of hypertension coupled with a lack of significant differences in vascular reactivity suggest that ET-1 is not the sole mediator of hypertension in this animal model. However, the tissue-specific changes in immunoreactive ET-1RP and 125I-labelled ET-1 binding sites suggest that ET-1 may be a partial mediator of hypertension and is subject to compensatory changes in response to the increased total peripheral resistance in SHR rats.Key words: endothelin, hypertension, spontaneously hypertensive rat.