Decrease in Circulating and Urine Adrenomedullin Concentrations in Stroke-Prone Spontaneously Hypertensive Rats.

Abstract

Adrenomedullin(AM) is a peptide with potent vasodilatory and hypotensive properties. Plasma AM levels in rats with experimentally induced hypertension, such as Dahl salt-sensitive rats and two-kidney, one-clip hypertensive rats, are higher than those in normotensive rats. We previously noted, however, that plasma AM levels in spontaneously hypertensive rats (SHR) are similar to those in Wistar-Kyoto rats. To define the role of AM in rats with severe hypertension, we investigated changes in circulating and tissue AM levels in stroke-prone spontaneously hypertensive rats (SHRSP/Izm Adrenomedullin (AM) is a novel hypotensive peptide discovered in human pheochromocytoma tissue by monitoring activity with respect to increasing cyclic adenosine monophosphate (cAMP) in rat platelets (1). AM consists of 52 amino acids with an intramolecular disulfide bridge. It shares slight homology with calcitonin gene-related peptide (CGRP). Appreciable concentrations of AM are found in normal human plasma and urine (2, 3). Furthermore, abundant AM mRNA is expressed in the adrenal medulla, heart, lung, and kidney in both humans and rats (2, 4). The intravenous injection of AM elicits potent, long-lasting, vasodilating and hypotensive effects in anesthetized rats (5). Ishimitsu et al. have reported that plasma AM levels are higher in patients with essential hypertension than in normotensive subjects. Moreover, the plasma AM level positively correlates with the severity of hypertension (6). These findings suggest that AM may act as a circulating hormone in the regulation of blood pressure. Shimokubo et al. (7) reported that the plasma AM levels in spontaneously hypertensive rats (SHR) were not higher than those in Wistar-Kyoto rats (WKY). However, there is no report on the circulating and tissue AM levels in stroke-prone spontaneously hypertensive rats (SHRSP/Izm), and the pathophysiological role of AM in severe hypertension is still obscure. As the first step in elucidating the pathophysiological role of AM in severe hypertension, we measured plasma, urine, and tissue AM levels and AM gene expression in 15-wk-old SHRSP/Izm, and compared the results with those in age-matched Wistar-Kyoto rats (WKY/Izm). Methods AnimalsWe used 15-wk-old male SHRSP/Izm (n = 8) and age-matched male WKY/Izm (n = 8) for measurement of immunoreactive rat AM (ir-rAM) and for RNA blot analysis. All rats were obtained from the

Failure of Probucol to Prolong Survival in Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats.

“…Male SHRSP/Izm (17,18) were obtained from the Disease Model Cooperative Research Association (Kyoto, Japan) at 8 weeks of age. The animals were housed in a specific-pathogen-free environment and given free access to standard rat chow (CE-2, 0.26% sodium; Japan Clea Co., Ltd., Tokyo, Japan) and tap water.…”

Proadrenomedullin N-Terminal 20 Peptide (PAMP) Immunoreactivity in Vertebrate Juxtaglomerular Granular Cells Identified by Both Light and Electron Microscopy

“…This peptide appears to be also closely associated to renal hypotensive activity (Ishimitsu et al, 1994;Khan et al, 1997;Hirano et al, 1998;Lai et al, 1998) and to natriuretic and diuretic effects under both pathological and normal conditions (Vari et al, 1996;Eto et al, 1996;Khan et al, 1997;Samson, 1998). Natriuretic and diuretic renal activities have also been observed for PAMP .…”