Angiotensins differentially activate phospholipase D in vascular smooth muscle cells from spontaneously hypertensive and Wistar-Kyoto rats.

We previously showed that angiotensin (Ang) II activates phospholipase D (PLD) through AT1 receptors in vascular smooth muscle cells (VSMC) isolated from Sprague-Dawley rats [Freeman and Tallant, Biochem J. 304:543-548, (1994)]. In the present study, we compared activation of PLD by angiotensin peptides in VSMC from spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto (WKY) rats. Ang II caused a dose-dependent increase in PLD activity in VSMC from both rat strains. However, the response to Ang II in VSMC from hypertensive rats was approximately three times higher than that observed in VSMC from normotensive controls. Furthermore, Ang II-induced activation of PLD in VSMC from hypertensive rats was significant within 1 min, whereas significant increases in PLD activity in cells from normotensive rats were not seen until 10 min after exposure to Ang II. Ang-(2-8) caused a similar increase in PLD activity which was three times higher in SHR VSMC than in WKY controls. In contrast, Ang-(1-7) did not affect PLD activity in either smooth muscle cell population. The Ang II-mediated increases in PLD activity in VMSC from both rat strains were completely blocked by AT1 receptor antagonists (EXP 3174 or L-158,809). Conversely, the AT2 receptor antagonist PD 123177 (1 mumol/L) was ineffective. Thus Ang II stimulation of PLD in VSMC derived from both the hypertensive and normotensive rat aorta and the accumulation of its metabolites (e.g., phosphatidic acid and diacylglycerol) is coupled to activation of AT1 receptors predominantly and occurs in response to Ang II or Ang-(2-8) but not Ang-(1-7). Moreover, activation of PLD by angiotensins in VMSC from the SHR is significantly more robust than that observed in VSMC from the normotensive WKY rat. We conclude that increased activation of PLD by Ang II in genetically-induced hypertension may reflect an additional mechanism linking enhanced contractile responses to enhanced growth.