Changes in Myogenic Tone in Spontaneously Hypertensive Rat: Role of RhoA and Protein Kinase C

ABSTRACT

BACKGROUND AND OBJECTIVES: The myogenic response was originally described as a contraction of a blood vessel that occurred following an increase in intravascular distending pressure. Conversely, a reduction in intravascular pressure produces myogenic vascular relaxation. Recent attention has focused on the potential role of this myogenic mechanism in the control of tone in the resistance vasculature, and in particular on how this mechanism may contribute to the increased vascular resistance seen in hypertension. Therefore, in the present study, we investigated the role of myogenic tone in the generation and/or maintenance of hypertension. MATERICAL AND METHODS: Myogenic tone was developed by stretching of the basilar arteries of WKY (istar Kyoto rat) and SHR (spontaneously hypertensive rats). Contractile responses, PKC (protein kinase C) immunoblots and translocation of PKC and RhoA were measured. In the presence of extracellular Ca2+ the stretching of the resting vessel evoked a myogenic contraction in the basilar arteries of SHR and WKY. Myogenic tone was significantly greater in SHR than in WKY. However, in the absence of extracellular Ca2+, stretching evoked a myogenic contraction in SHR, but not in WKY. The stretch-induced myogenic tone was inhibited by nifedipine. The effect of nifedipine was similar in both SHR and WKY rats. H-7, calphostin C and Y-27632, also inhibited stretch-induced myogenic tone in both SHR and WKY. The inhibitory effects of these drugs were greater in SHR than in WKY. Immunoblotting showed rho A and PKC alpha were translocated from the cytosol to the cell membrane with stretching in both SHR and WKY. PKC beta, however, was translocated to the cell membrane with stretching in SHR, but not in WKY. CONCLUSION: These results suggest that stretch-induced myogenic tone is significantly greater in SHR than in WKY. Furthermore, the increase in amount and/or activity of PKC beta and ROK (rhoA-associated kinase) may be a key mechanism accounting for the enhanced myogenic tone in SHR.