Abstract
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.
Highlights
Men have a greater incidence and severity of cardiovascular disease compared to women until menopause (Gerhard and Ganz 1995; Wiinberg et al 1995)
The molecular mechanisms responsible for sex differences in cardiovascular health and function are still unclear, the nitric oxide (NO)/NO synthase (NOS) pathway has been implicated in humans (Forte et al 1998; Sader and Celermajer 2002) and rats (Baylis et al 1992; Ribeiro et al 1992; Kauser and Rubanyi 1994, Gamboa et al 2007) and we recently published that female spontaneously hypertensive rats (SHR) are more dependent on NOS to maintain their blood pressure than males (Brinson et al 2013)
The current study examined the impact of both sex and blood pressure status on vascular function
Summary
Men have a greater incidence and severity of cardiovascular disease compared to women until menopause (Gerhard and Ganz 1995; Wiinberg et al 1995). A similar sex disparity in cardiovascular disease is seen in a number of experimental animal models of hypertension, including spontaneously hypertensive rats (SHR) (Kauser and Rubanyi 1995; Iliescu et al 2006). The molecular mechanisms responsible for sex differences in cardiovascular health and function are still unclear, the nitric oxide (NO)/NO synthase (NOS) pathway has been implicated in humans (Forte et al 1998; Sader and Celermajer 2002) and rats (Baylis et al 1992; Ribeiro et al 1992; Kauser and Rubanyi 1994, Gamboa et al 2007) and we recently published that female SHR are more dependent on NOS to maintain their blood pressure than males (Brinson et al 2013).
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