Evidence for protein kinase C involvement in arteriolar myogenic reactivity

Abstract

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)

Crosstalk between Gi and Gq/Gs pathways in airway smooth muscle regulates bronchial contractility and relaxation

“…PKCα was upregulated by approximately 50% (P < 0.01) in G αi2 -IP cells but unchanged in G αi2 -OE cells ( Figure 6B). Given that PKCα has been demonstrated to sensitize smooth muscle to contraction (12)(13)(14)(15), this upregulation in the G αi2 -IP cells is consistent with the hyperresponsive contractile phenotype. Less is known about the other PKC isoforms in regards to G protein-coupled receptor-mediated smooth muscle contraction.…”

“…In a positive feedback loop, PKCα sensitizes smooth muscle to receptor-mediated contraction via G q receptors. This effect has been particularly well documented in vascular smooth muscle, where PKC increases the myofilament force sensitivity to intracellular Ca 2+ concentration (12)(13)(14)(15). Interestingly, increased G αi has been reported in many animal models of cardiac hypertrophy and heart failure (18)(19)(20) as well as in human heart failure (21).…”

Involvement of Metalloproteinases 2/9 in Epidermal Growth Factor Receptor Transactivation in Pressure-Induced Myogenic Tone in Mouse Mesenteric Resistance Arteries

“…One attractive candidate is PKC, because several studies have found that PKC inhibitors block MT in cerebral arteries 24 and skeletal muscle arterioles. 25 Recently, Koller's laboratory reported that p38 and ERK1/2 MAP kinase inhibitors are partially involved in pressure-induced MT in rat skeletal muscle arterioles. 26 Conversely, Spurrel et al 27 have shown that ERK1/2 phosphorylation is apparently dissociated from the mechanisms directly contributing to the acute myogenic contractile response.…”

Pressure-induced myogenic tone and role of 20-HETE in mediating autoregulation of cerebral blood flow

“…20-hydroxyeicosatetraenoic acid; cytochrome P-450 4A; ion channels; membrane potential STEPWISE INCREASE OF transmural pressure in isolated and cannulated cerebral arteries gives rise to a series of signaling events that culminate in stepwise constriction of the arterial segments. These arterial muscle signaling events include membrane depolarization, reduction in outward K ϩ current, increase in inward Ca 2ϩ current (via L-type Ca 2ϩ channels), translocation of PKC and phosphorylation, and elevation of inositol 1,4,5-trisphosphate and diacylglycerol, all of which are related to the activation of arterial muscle and allow arterial diameter to track changes in blood pressure, thereby maintaining blood flow relatively constant (3, 5,19,25,(27)(28)(29)(30)(31)44). The signaling pathway mediating these events involves the production of the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) (15,21,23,26,34).…”