Role of protein kinase C in myogenic calcium-contraction coupling of rat cannulated mesenteric small arteries.
1. The present study was designed to determine the role of protein kinase C (PKC) in the myogenic response of small arteries. In particular, we tested whether inhibition of PKC reverses the previously found pressure-induced elevation of contractile element calcium sensitivity. 2. Rat mesenteric small arteries were cannulated and pressurized. The internal diameter was continuously monitored with a video camera and intracellular calcium levels were measured by means of fura-2. Myogenic responses were observed when the pressure was raised stepwise from 20 to 60 and then to 100 mmHg in physiological saline solution and during application of phenylephrine (0.1 or 1 micromol/L) or potassium (36 mmol/L). 3. The PKC inhibitors H-7 (20 micromol/L), staurosporine (100 nmol/L) and calphostin C (10 nmol/L) all completely abolished the myogenic response. Whereas staurosporine caused an ongoing reduction in intracellular calcium, pressure-induced calcium transients were not affected by either H-7 or calphostin C. In particular, the slope of the wall tension-calcium relationship remained similar in the presence of both H-7 and calphostin C, despite an upward shift of this relationship to higher calcium levels in the case of calphostin C. 4. These results show that activity of PKC isoform(s) is essential for myogenic calcium-contraction coupling.
Wesselman
J P
JP
Department of Medical Physics and Cardiovascular Research Institute Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Spaan
J A
JA
van der Meulen
E T
ET
VanBavel
E
E
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002404:Catheterization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology; D013256:Steroids; D014661:Vasoconstriction / Q000187:drug effects
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D012503:Saponins; D013256:Steroids; C404167:stauntoside B; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; C058819:calphostin C; D002118:Calcium