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(Hypertension. 1996;28:772-778.)
© 1996 American Heart Association, Inc.

Articles

Angiotensin II–Stimulated Phospholipase C Responses of Two Vascular Smooth Muscle–Derived Cell Lines

Role of Cyclic GMP

Richard J. Baines; Colin Brown; Leong L. Ng; Michael R. Boarder

the Departments of Cell Physiology and Pharmacology and of Medicine and Therapeutics (L.L.N.), School of Medicine, University of Leicester (UK).

Vascular smooth muscle cells of the spontaneously hypertensive rat (SHR) are known to show increased responsiveness to angiotensin II (Ang II) compared with cells of normotensive control Wistar-Kyoto rats (WKY). We investigated the hypothesis that differential levels of cGMP lead to the different responsiveness of the cells, using vascular smooth muscle cells in culture. cGMP levels in extracts of SHR-derived cells were lower than those of WKY-derived cells. This was true for both unstimulated cells and cells treated with equal concentrations of either sodium nitroprusside or S-nitroso-N-acetylpenicillamine. Stimulation of cells with Ang II did not affect levels of cGMP but increased levels of inositol 1,4,5-trisphosphate (IP₃) and Ca²⁺, which were greater in SHR- than in WKY-derived cells. When SHR and WKY cells were preincubated with different concentrations of S-nitroso-N-acetylpenicillamine to generate similar cGMP levels in each cell type, the subsequent IP₃ response to Ang II was the same in the two cell types. To reduce any influence of cGMP on responses, we permeabilized the cells with -toxin. Stimulation of -toxin–permeabilized cells with high Ca²⁺ revealed an IP₃ response in SHR- but not WKY-derived cells. Similarly, permeabilized SHR cells responded to Ang II but WKY cells did not. However, GTP and GTPS elevated IP₃ in both cell types. Taken together, these results indicate that the low response of WKY cells can be accounted for by the inhibitory influence of cGMP. However, when this inhibition is removed by permeabilization, further differences between the cells are revealed that will contribute to the elevated SHR response.

Key Words: muscle, smooth vascular • rats, inbred SHR • angiotensin II • cyclic GMP • phospholipase C

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