The present study tested the hypothesis that spontaneously hypertensive rats (SHR) have impaired nitric oxide synthase (NOS)-mediated regulation of vascular function versus Wistar-Kyoto rats (WKY). Aorta and small mesenteric arteries were studied from male and female SHR (M SHR and F SHR) and WKY (M WKY and F WKY). Phenylephrine (PE)-induced vasoconstriction was greater in aorta of M SHR versus all others (P < 0.05); there were neither sex nor strain differences in PE contraction in mesenteric arteries. The NOS inhibitor l-Nitro-Arginine Methyl Ester (l-NAME) increased PE-induced vasoconstriction in all rats, although the increase was the least in male SHR (P < 0.05), revealing a blunted vasoconstrictor buffering capacity of NOS. l-NAME increased sensitivity to PE-induced constriction only in mesenteric arteries of SHR, although, the maximal percent increase in contraction was comparable among groups. ACh-induced relaxation was also less in aorta from M SHR versus all others (P < 0.05). ACh relaxation was comparable among groups in mesenteric arteries, although SHR exhibited a greater NOS component to ACh-induced relaxation than WKY. To gain mechanistic insight into sex and strain differences in vascular function, NOS activity and NOS3 protein expression were measured. Aortic NOS activity was comparable between groups and M SHR had greater NOS3 expression than M WKY. In contrast, although vascular function was largely maintained in mesenteric arteries of SHR, NOS activity was less in SHR versus WKY. In conclusion, M SHR exhibit a decrease in NOS regulation of vascular function compared to F SHR and WKY, although this is not mediated by decreases in NOS activity and/or expression.
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This work was supported by funds from the NIH Heart, Blood and Lung Institute (HL093271 to JCS and HL HL111354 to ASL), Bethesda, Maryland.
Loria, Analia S.; Brinson, Krystal N.; Fox, Brandon M.; and Sullivan, Jennifer C., "Sex-Specific Alterations in NOS Regulation of Vascular Function in Aorta and Mesenteric Arteries from Spontaneously Hypertensive Rats Compared to Wistar Kyoto Rats" (2014). Pharmacology and Nutritional Sciences Faculty Publications. 35.