Modulation of cerebral arteriolar diameter by intraluminal flow and pressure.
We determined whether cerebral arterioles in vitro adjust their diameters in response to changes in intraluminal flow rate and pressure. Intracerebral arterioles (38- to 55-microns diameter) were isolated from Sprague-Dawley rats and cannulated with a perfusion system that permitted separate control of intraluminal pressure and flow rates. Increasing pressure at 0 flow, in 20 mm Hg steps from 20 to 100 mm Hg, resulted in myogenic constriction, which was greatest at 60 mm Hg (approximately 20%). Increasing flow rate at a constant pressure of 60 mm Hg elicited a biphasic response. At flow rates of up to 10 microL/min, the arterioles dilated by up to 14.5 +/- 2.2% of their control diameter. At higher (> 10 microL/min) flow rates, however, a progressive restoration of resting diameter was observed. Application of the nitric oxide synthase inhibitor NG-mono-methyl-L-arginine (L-NMMA, 0.1 mmol/L) caused a 15.4 +/- 1.7% decrease in control diameter (at 60 mm Hg, zero flow). Although L-NMMA did not affect the responses to increases in pressure or to vasodilators (adenosine and pH 6.8 buffer), it abolished the dilator responses to flow rate increases and to acetylcholine. In contrast, inhibition of prostaglandin synthesis by indomethacin (10 mumol/L) had no effect on flow-induced dilation. These results show that changes in intraluminal flow rates and pressure can independently influence cerebral arteriolar tone and suggest that the flow-induced dilator responses of cerebral arterioles are mediated by an arginine metabolite, such as nitric oxide.
Ngai
A C
AC
Department of Neurological Surgery, University of Washington School of Medicine, Seattle, USA.
Winn
H R
HR
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D001120:Arginine; D007213:Indomethacin