Altered microvascular responses to C5a in rat striated muscle during two-kidney, one clip renovascular hypertension.
OBJECTIVE
To determine how two-kidney, one clip (2-K,1C) renovascular hypertension alters microvascular responses in rat striated muscle to complement C5a, one of the most important inflammatory mediators.


METHODS
2-K,1C hypertension was induced in male Sprague-Dawley rats. Under anesthesia with pentobarbital (50 mg/kg, intraperitoneally) the cremaster muscle microcirculatory preparation with intact neurovascular connections was studied in vivo by closed-circuit videomicroscopy. Recombinant human C5a was applied topically in the tissue bath at concentrations of 10(-12), 10(-10) and 10(-8) mol/l, consecutively. Changes in the microvessel diameters in small arterioles, large arterioles and venules were measured.


RESULTS
In normotensive rats complement C5a induces a significant dilation in small arterioles at low bath concentrations (10(-12) or 10(-10) mol/l), but the dilation is attenuated at a higher concentration (10(-8) mol/l). In contrast, in 2-K,1C hypertensive rats C5a constricts small arterioles at low concentrations (< 10(-10) mol/l) but dilates them at a higher concentration (10(-8) mol/l). Large arterioles and venules have minimal responses to C5a in either normotensive or 2-K,1C hypertensive rats.


CONCLUSIONS
2-K,1C hypertension dramatically alters C5a-induced microvascular responses in small arterioles. The alteration might be attributable to the enhanced vasoconstrictor mechanisms and impaired vasodilator mechanisms during 2-K,1C renovascular hypertension.
Yang
S
S
Department of Physiology and Biophysics, Health Science Center, University of Louisville, Kentucky, USA.
Luo
H Y
HY
Wilson
M A
MA
Wead
W B
WB
Harris
P D
PD
D000818:Animals; D015936:Complement C5a / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D015936:Complement C5a