Cerebral artery selective inhibition of protein kinase C-mediated contraction by HNS-32, a novel azulene-1-carboxamidine derivative

The vasorelaxant actions of a novel azulene-1-carboxamidine derivative, HNS -32, were investigated on the tension development evoked by phorbol 12, 13 dibutyrate (PDBu) in cerebral and femoral arteries isolated from the dogs. In basilar artery, HNS-32 inhibited almost completely PDBu-induced contract ion in a concentration-dependent manner with potency about 10 times stronge r than that of fasudil, a protein kinase inhibitor. In contrast, in femoral artery, HNS-32 failed to suppress the tension development in response to P DBu whereas fasudil inhibited it with a similar potency as in basilar arter y. These findings indicate that HNS-32 selectively suppresses cerebral arte ry contraction mediated via an activation of protein kinase C.