Abnormal vascular phosphoinositide hydrolysis in the spontaneously hypertensive rat

Abstract

1 The production of [3H]-inositol phosphates was studied in labelled segments of aorta from spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) controls at 5 and 19 weeks, either unstimulated or in the presence of noradrenaline. 2 Basal hydrolysis of inositol phospholipids was significantly enhanced in young SHR (P < 0.05) compared to controls but this difference was no longer detected at 19 weeks. 3 Noradrenaline increased [3H]-inositol phosphate accumulation in both SHR and WKY, but maximal hydrolysis was significantly greater in WKY (P <0.01), although the ED50 was similar in both groups of animals. 4 These data demonstrate that phosphatidylinositide hydrolysis is enhanced in the young hypertensive rat at the time blood pressure is rising, but that this activity has declined by the time hypertension has reached an established phase. In addition, a,-agonist induction of inositol phospholipid hydrolysis differs in the two species of animals, being reduced in genetically mature hypertensive rats.

Lipid composition and fluidity in the jejunal brush-border membrane of spontaneously hypertensive rats. Effects on activities of membrane-bound proteins

“…It is accepted that inositol lipids are involved in signal transduction events and that a possible link between a global disturbance of cell membrane lipids and cell function, through membrane-based second messenger systems, may occur (23). In addition, disturbances of the phosphoinositide turnover have been reported in early stages of hypertension in SHR and man (24,25). However, we have not found differences in the level of PI in either group of animals.…”

Mitogen-Activated Protein/Extracellular Signal–Regulated Kinase Inhibition Attenuates Angiotensin II–Mediated Signaling and Contraction in Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

“…In cultured vascular smooth muscle cells from adult SHR, Ang IIstimulated phospholipase C-mediated signaling is increased, with augmentation of [Ca 2ϩ ] i and pH i responses relative to normotensive controls. 5,10 These effects are partially due to increased Ca 2ϩ influx and mobilization and to enhanced activity to the Na ϩ -H ϩ exchanger. 11,12 [Ca 2ϩ ] i elevation and alkalinization are major determinants of vascular contraction.…”

Differences in inositol phosphate production in blood vessels of normotensive and spontaneously hypertensive rats

“…Nevertheless when the a2-adrenoceptor antagonist rauwolscine (10-6_0-5 M) was present, the contractile concentration-response curve was clearly shifted to the right and the maximum obtained was again at 10-3 M (Edvinsson et al, 1989 (Eid & De Champlain, 1988) or the mesenteric artery (Takata et al, 1989) of DOCA-salt rats compared to controls. In the aorta of 5 week-old SHR the basal activity was higher than in agematched WKY rats but this difference was no longer apparent when the hypertension was established (Heagerty et al, 1986 (Heagerty et al, 1986). In addition, isometric contractions of aortic rings as well as incorporation of "P-phosphate into phosphatidic acd induced by noradrenaline was greater in WKY than in agematched SHR (Ek et al, 1989;Aidulis et al, 1990).…”