INCREASED CA2-KINASE-C IN ALPHA-TOXIN-PERMEABILIZED SMA FROM YOUNG SPONTANEOUSLY HYPERTENSIVE RATS( SENSITIVITY OF CONTRACTILE ELEMENTS VIAPROTEIN)

Objective: The purpose of the present investigation was to examine the Ca2+ sensitivity of the contractile elements via protein kinase C (PK C) in superior mesenteric artery (SMA) from young (5-6 weeks old) spon taneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats ( WKY), Methods: Staphylococcal aureus a-toxin, which produces pores in the plasma membrane too small to allow passage of proteins such as PKC , was used to investigate the signal transduction system in vascular s mooth muscle cells, We investigated the Ca2+ sensitivity of the contra ctile apparatus via PKC in intact and cu-toxin skinned SMA from young SHR and WKY. Results: In intact SMA, high K+ responses were not differ ent between SHR and WKY. However. phorbol 12,13-dibutyrate (PDBu, a PK C activator) augmented high K+-evoked contractions and PKC inhibitors, such as 1-(5-isoquinolinesulfonyl)-2-methylpiper (H-7) and calphostin C, suppressed them more in SHR as compared with WKY. In alpha-toxin s kinned SMA, the [Ca2+](i)-force relationship curve was not significant ly different between SHR and WKY. However, PDBu augmented [Ca2+](i)-ev oked contractions and PKC inhibitors suppressed them more in SHR than in WKY. Conclusion: These results suggest that the Ca2+ sensitivity of the contractile elements via PKC is significantly greater in prehyper tensive SHR than in age-matched WKY. This abnormality in small muscula r arteries may be involved in the pathogenesis of hypertension in SHR. (C) 1997 Elsevier Science B.V.