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Inactivation of Enhanced Expression of G_i Proteins by Pertussis Toxin Attenuates the Development of High Blood Pressure in Spontaneously Hypertensive Rats

From the Department of Physiology and Groupe de Recherche sur le Système Nerveux Autonome, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.

Correspondence to Dr Madhu B. Anand-Srivastava, Department of Physiology, Faculty of Medicine, University of Montreal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, Canada H3C 3J7. E-mail anandsrm{at}physio.umontreal.ca

We have previously shown that the enhanced expression of G_i proteins in spontaneously hypertensive rats (SHR) that precedes the development of high blood pressure may be one of the contributing factors in the pathogenesis of hypertension. In the present study, we demonstrate that the inactivation of G_i proteins by intraperitoneal injection of pertussis toxin (PT, 1.5 µg/100 g body wt) into 2-week-old prehypertensive SHR prevented the development of hypertension up to 4 weeks and that, thereafter, it started to increase and reached the same level found in untreated SHR after 6 weeks. A second injection of PT after 4 weeks delayed the increase in blood pressure for another week. The PT-induced decrease in blood pressure in 6-week-old SHR was associated with a decreased level of G_i-2 and G_i-3 proteins in the heart, as determined by in vitro ADP ribosylation and immunoblotting. The decreased level of G_i proteins was reflected in decreased G_i functions. Furthermore, an augmentation of blood pressure to the same level in PT-treated SHR as found in untreated SHR was associated with enhanced expression and function of G_i. These results indicate that the inactivation of G_i proteins by PT treatment in prehypertensive SHR attenuates the development of hypertension and suggest that the enhanced levels of G_i proteins that result in the decreased levels of cAMP and associated impaired cellular functions may be contributing factors in the pathogenesis of hypertension in SHR.

Key Words: pertussis toxin • ADP ribosylation • G proteins • blood pressure • spontaneously hypertensive rats

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