Second messenger systems: functional role in cerebrovascular smooth muscle regulation.
The role of two second messenger systems in alterations of cerebrovascular smooth muscle tone was examined in feline cerebral arteries using an in vitro preparation of vessel segments and cortical pial vessels in situ. Forskolin, which is known to activate adenylate cyclase, elicited a concentration-dependent relaxation of arteries preconstricted with prostaglandin F2 alpha (PGF2 alpha) (EC50 was approximately 300 nM). Microapplication of forskolin around individual cortical arteries and arterioles in situ elicited a dose-dependent dilatation. The maximum increase in arteriolar calibre was 54 +/- 4% from pre-injection calibre and EC50 was approximately 100 nM. Phorbol 12,13 dibutyrate (PDBu), which activates protein kinase C, elicited strong contractions of cerebral vessels. In vitro, PDBu contracted vessel segments in a concentration-dependent manner (EC50 was approximately 100 nM). Similarly, PDBu elicited potent dose-dependent constriction of pial arterioles in situ. The maximum response to PDBu was a 37 +/- 5% reduction in arteriolar calibre and the concentration eliciting EC50 was approximately 100 nM. These data provide an assessment to capacity of feline cerebral arteries to dilate and contract in response to adenylate cyclase and protein kinase C activation respectively.
Horsburgh
K
K
Wellcome Surgical Institute and Hugh Fraser Neuroscience Laboratories, University of Glasgow, U.K.
Jansen
I
I
Edvinsson
L
L
McCulloch
J
J
D000818:Animals; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D002550:Cerebral Veins / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology*; D015237:Dinoprost / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D015290:Second Messenger Systems / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D015237:Dinoprost