Protein kinase C modulates basal myogenic tone in resistance arteries from the cerebral circulation.
The objective of this study was to determine whether myogenic tone in the cerebral circulation can be modified by agents that interact with protein kinase C (PKC), a modulator of intracellular calcium sensitivity. Pial arteries (194 +/- 8 microns at 125 mm Hg) were isolated from Wistar-Kyoto rats and mounted on glass microcannulas in a specialized arteriograph. Simultaneous recordings of transmural pressure and lumen diameter were made with a video-electronic system. Myogenic tone, which developed at transmural pressures above 50 mm Hg, reduced lumen diameter by 29 +/- 3%, to 136 +/- 5 microns. Staurosporine (a PKC inhibitor) or indolactam (a PKC activator) was added cumulatively to segments of arteries obtained from each animal. Staurosporine induced progressive and eventually complete dilation, with half-maximal inhibition of myogenic tone occurring at a concentration of 1.32 +/- 0.10 nM. Conversely, indolactam augmented basal tone, reducing diameter by a maximum of 62 +/- 3%, with half-maximal effects at 0.4 +/- 1.0 microM. The effects of indolactam on arterial responses to acute increases in transmural pressure were also determined to test whether this dynamic and possibly separate mechanism could be potentiated by PKC stimulation. Although basal tone was augmented, diameter responses to increased pressure were not altered. In summary, these results implicate PKC in the regulation of basal myogenic tone and resistance artery caliber, which is a major determinant of blood flow. PKC modulation did not affect diameter responses to sudden changes in transmural pressure, however, suggesting the existence of a separate sensing/transduction mechanism that has yet to be identified.
Osol
G
G
Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington 05405.
Laher
I
I
Cipolla
M
M
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D007769:Lactams / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011312:Pressure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D019311:Staurosporine; D014655:Vascular Resistance; D014661:Vasoconstriction; D014666:Vasomotor System / Q000502:physiology*
D000470:Alkaloids; D007211:Indoles; D007769:Lactams; D011493:Protein Kinase C; D019311:Staurosporine; D011188:Potassium