Gender differences in mesenteric vasoconstrictor reactivity following chronic hypoxia.
Male rats demonstrate persistent endothelium-dependent attenuation of vasoconstrictor reactivity following chronic hypoxia (CH). Since estrogen may interfere with hypoxia-induced gene expression, we hypothesized that gender differences exist in this response to CH. However, in conscious, instrumented rats, we found that CH resulted in a similar persistent reduction of pressor/total peripheral resistance responses to phenylephrine (PE) in rats of both genders. In contrast, although previous studies show mesenteric vascular responses to PE are reduced in CH males, we found that mesenteric reactivity was maintained in CH females. Since normoxic females demonstrate greater nitric oxide (NO) production, we hypothesized that the failure of CH to further diminish mesenteric reactivity in females was due to the inhibition of NO-dependent vasodilation. To test this hypothesis, constrictor reactivity of mesenteric arteries from male and female rats was examined. NO synthase (NOS) inhibition augmented constrictor responses to PE in arteries from both normoxic and CH males and normoxic females. In contrast, NOS inhibition had no effect in CH female vessels. Endothelial NOS (eNOS) levels were not different in arteries from control and CH females. Endothelial [Ca2+]i was greater in arterioles from CH females. Thus, CH reduces NO-dependent mesenteric dilation in females; this effect is not due to altered eNOS levels or diminished endothelial [Ca2+]i.
Gonzales
Rayna J
RJ
Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA. rjgonzal@arizona.edu
Bryant
Jessica M
JM
Naik
Jay S
JS
Resta
Thomas C
TC
Walker
Benjimen R
BR
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002908:Chronic Disease; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D000860:Hypoxia / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D008638:Mesenteric Arteries / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology
D004967:Estrogens; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D002118:Calcium