Regional differences in the expression of nitric oxide synthase and specific receptors in the vascular tissues of control and diabetic rabbits: a pilot study.
BACKGROUND
Atherosclerosis can influence the expression of endothelial nitric oxide synthase (eNOS) as well as endothelin-1 (ET-1) and 5-hydroxytryptamine (5HT; serotonin) receptors. Diabetes has an effect on the onset, severity and pattern of atherosclerosis with a predilection for more distal arteries. We aimed to identify regional differences in the distribution of eNOS activity, ET-1 and 5HT receptors in vascular tissues obtained from control and diabetic rabbits.


METHODS
The mid abdominal aorta, right renal and right femoral arteries were harvested from 12 adult rabbits (6 months old, 3-3.9 kg); 8 controls and 4 diabetic (induced using alloxan 7 months previously). Samples were stored in liquid nitrogen for Western immunoblotting for eNOS as well as ET-1 and 5HT receptors.


RESULTS
Significant differences were found in the distribution of eNOS, ET-1 and 5HT between the aorta, renal and femoral arteries in the controls. The number of ET-1 receptors was significantly higher (aorta; p=0.016, renal; p=0.004, femoral; p=0.05,) whereas, the expression of eNOS was significantly lower (aorta; p =0.004, renal; p =0.004, femoral; p =0.008) when comparing arteries from normal rabbits with these from diabetics ones. The number of 5HT receptors was higher in arteries from diabetic rabbits but this was not statistically significantly.


CONCLUSIONS
The "regional" distribution of eNOS activity as well as ET-1 and 5HT receptors in control rabbits varies significantly according to the vessel assessed. Further studies are needed to evaluate the effect of blocking these receptors (e.g. on the risk of re-stenosis). Regional receptor differences may explain why diabetes is linked with a predilection for atherosclerosis (and possibly calcification) in distal arteries.
Alnaeb
M E
ME
Vascular Unit, Royal Free Hampstead NHS Trust Hospital, London, UK.
Thompson
C S
CS
Seifalian
A M
AM
Hamilton
G
G
Mikhailidis
D P
DP
D000818:Animals; D001808:Blood Vessels / Q000201:enzymology*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010865:Pilot Projects; D011817:Rabbits; D044022:Receptor, Endothelin A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*
D044022:Receptor, Endothelin A; D011985:Receptors, Serotonin; D052250:Nitric Oxide Synthase Type III