L-arginine and antineutrophil serum enable venular control of capillary perfusion in hypercholesterolemic rats.
OBJECTIVE
The purpose of this study was to investigate and counteract dysfunctional control of capillary flow in hypercholesterolemia. Capillary flow is controlled by arteriolar tone, which in turn is influenced by mediators released from closely paired venules in a mechanism that involves nitric oxide (NO). However, venular control of capillary flow is altered with hypercholesterolemia.


METHODS
Rats were given a normal or high-cholesterol diet before measurements of mesenteric capillary red blood cell velocity. The arteriolar pathway leading to the capillary was videotaped to measure the percent of the surrounding area (within 15 |gmm) that was occupied by a venule (% pairing).


RESULTS
Venule-paired arterioles were significantly smaller in hypercholesterolemia compared with normocholesterolemia, corresponding to slower capillary flow. A positive correlation between capillary velocity and % pairing observed in normocholesterolemia was not observed during NO synthase inhibition or in hypercholesterolemic rats. However, positive correlations between the two parameters were found in hypercholesterolemia when the rats were given drinking water supplementation of L-arginine or an injection of antineutrophil serum, both of which tended to improve velocity in capillaries branching from venule-paired arteriolar pathways.


CONCLUSIONS
Dysfunctional venular control of capillary perfusion in hypercholesterolemia may be a consequence of a neutrophil-mediated deficiency of NO.
Nellore
Kavitha
K
Bioengineering Department, Pennsylvania State University, University Park, PA, USA.
Harris
Norman R
NR
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects / Q000502:physiology*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology*; D007106:Immune Sera / Q000494:pharmacology; D007962:Leukocytes / Q000276:immunology / Q000502:physiology; D008297:Male; D018715:Microscopy, Video; D009569:Nitric Oxide / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D014699:Venules / Q000187:drug effects* / Q000502:physiology
D019268:Antibodies, Antineutrophil Cytoplasmic; D007106:Immune Sera; D009569:Nitric Oxide; D001120:Arginine