Evidence for protein kinase C involvement in arteriolar myogenic reactivity.
Little information exists as to the cellular events that couple the myogenic contractile response of an arteriole to an acute rise in intravascular pressure. The aim of this study was to examine whether protein kinase C (PKC), which has been implicated in the contractile response to agonists, contributes to myogenic vasoconstriction of cremaster muscle arterioles. Studies were performed on anesthetized rats, enclosed in an airtight Plexiglas box, with the cremaster exteriorized into a bath containing Kreb's solution. Pressure in the box was increased to elevate intravascular pressure by 20 mmHg. To examine PKC involvement, studies were performed in the absence or presence of inhibitors of PKC: H 7 (10(-9)-10(-5) M) or staurosporine (10(-10)-10(-7) M). Inhibitors were added to the tissue bath and produced no observable systemic effects or alterations in arteriolar diameter. Third-order arteriole (16 +/- 1 microns diam) responses to these agents and alterations in intravascular pressure were monitored by in vivo microscopy and vessel diameter was measured with a video caliper. H 7 produced a concentration-dependent inhibition of myogenic vasoconstriction, inhibiting the extent of constriction by 75% at 10(-5) M. Similarly, staurosporine caused a concentration-dependent inhibition of pressure-induced constriction. At 10(-7) M staurosporine the myogenic response was inhibited by 82%. Further support for a role for PKC in the myogenic response was provided by the observation that indolactam (10(-6) M), a stimulator of PKC activity, induced myogenic reactivity in first-order arterioles, which under basal conditions show passive distension to increased intravascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Hill
M A
MA
Microcirculation Research Institute, College of Medicine, Texas A & M University, College Station 77843.
Falcone
J C
JC
Meininger
G A
GA
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007769:Lactams / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction
D007211:Indoles; D007769:Lactams; C043969:indolactam V; D011493:Protein Kinase C