ENHANCED VASCULAR REACTIVITY TO MASTOPARAN, A G-PROTEIN ACTIVATOR, INGENETICALLY HYPERTENSIVE RATS

Vascular smooth muscle from stroke-prone spontaneously hypertensive ra ts has an increased responsiveness to the vasoconstrictors angiotensin II and serotonin. This abnormality is postulated to contribute to the hypertension characteristic of this strain of rats. We hypothesized t hat a portion of the increased responsiveness may be due to altered fu nction of G proteins. This hypothesis was tested using mastoparan, a p eptide that mimics ligand-bound receptors to stimulate G proteins dire ctly. In addition, we investigated the mechanism of mastoparan-induced contraction of vascular smooth muscle. Changes in isometric tension w ere recorded in denuded carotid artery strips from hypertensive and no rmotensive (Wistar-Kyoto) rats. Vascular strips from the hypertensive rats had a significantly greater response to mastoparan at all concent rations between 10(-8) and 10(-5) mol/L. A G protein inhibitor, N-ethy lmaleimide (10(-3) mol/L), attenuated the response to mastoparan (10(- 7) mol/L) (67+/-4% of control response), whereas pertussis toxin treat ment did not. Inhibition of phospholipase C also significantly decreas ed the mastoparan-induced response (23+/-12% of control), and nifedipi ne (10(-3) mol/L), a calcium channel blocker, completely blocked the m astoparan-induced contraction. Indomethacin treatment did not affect t he mastoparan contraction even though mastoparan has been shown to sti mulate phospholipase A(2) in other cell types. In conclusion, we obser ved an increased response in carotid arteries from genetically hyperte nsive rats to a pharmacological intervention that appears to act via G protein-linked phospholipase C stimulation and L-type calcium channel activation, suggesting that the increased vascular reactivity in stro ke-prone spontaneously hypertensive rats is due in part to altered fun ction of G proteins.