Sex-specific alterations in NOS regulation of vascular function in aorta and mesenteric arteries from spontaneously hypertensive rats compared to Wistar Kyoto rats

Loria, Analia S.; Brinson, Krystal N.; Fox, Brandon; Sullivan, Jennifer C.

doi:10.14814/phy2.12125

Cited by 28 publications

(25 citation statements)

References 55 publications

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“…These findings indicate that the dependence of molecular mechanisms regulating vascular tone on sympathetic innervation differs between renal and mesenteric arteries. In agreement with other studies [35,36], our experiments did not reveal sexspecific differences of norepinephrine sensitivity in small arteries. We did not observe sex-specific effects of sympathectomy on the pharmacological characteristics of the arteries investigated suggesting that long-term effects of sympathetic innervation on these blood vessels are similar in male and female rats.…”

Section: Discussionsupporting

confidence: 94%

Sympathetic denervation facilitates L-type Ca2+ channel activation in renal but not in mesenteric resistance arteries

Heumann

Koenen²,

Zavaritskaya³

et al. 2016

Journal of Hypertension

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Section: Discussionsupporting

confidence: 94%

Sympathetic denervation facilitates L-type Ca2+ channel activation in renal but not in mesenteric resistance arteries

Heumann

Koenen²,

Zavaritskaya³

et al. 2016

Journal of Hypertension

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“…In the present study, we found no differences in VR between vehicle-treated young males and females. This response is in agreement with previous reports (Júnior and Cordellini, 2007 ; Loria et al, 2014 ).…”

Section: Discussionsupporting

confidence: 94%

Age-, Gender-, and in Vivo Different Doses of Isoproterenol Modify in Vitro Aortic Vasoreactivity and Circulating VCAM-1

et al. 2018

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Different human-like cardiomyopathies associated to β-adrenergic stimulation are experimentally modeled in animals through variations in dose, route, and duration of administration of different cardiotoxic drugs. However, associated changes in the vasculature and their relation to systemic inflammation, and the influence of cardiovascular diseases risk factors (gender and age) upon them are seldom analyzed. Here we studied the effect of age and gender on the vasoreactivity of aortas from mice subjected to in vivo repeated β-adrenergic stimulation with different doses of isoproterenol (ISO) in association with circulating inflammatory cytokines. Young (2 months) and old (18 months) male and female mice received 0 (control), 5, 40, 80 or 160 μg/g/d of ISO (7 days, s.c.). IL-1α, IL-4 and vascular cell adhesion molecule-1 (VCAM-1) were quantified in plasma. In vitro, norepinephrine-induced vasoconstriction and acetylcholine-induced relaxation were measured in aortas. No differences in contraction, relaxation, IL-1α, and IL-4 were found between control young males and females. Age decreased contraction in males and relaxation was lower in females and abolished in males. VCAM-1 was higher in young males than in females and increased in old mice. Vasoconstriction in ISO-treated mice results as a bell-shaped curve on contraction in young and old males, with lower values in the latter. In females, ISO-160 increased contraction in young females but decreased it in old females. Vasorelaxation was reduced in ISO-treated young males and females. ISO-80 and 160 reduced vasorelaxation in old females, and intermediate doses relaxed aortas from old males. VCAM-1 was higher in young and old males with ISO-80 and 160; while VCAM-1 was higher only with ISO-160 in old females. Our results demonstrate that repeated β-adrenergic stimulation modifies vascular reactivity depending on gender, age, and dose. Females were less sensitive to alterations in vasoreactivity, and young females required a higher amount of the adrenergic stimuli than old females to show vascular alterations. Changes were independent of IL-1α and IL-4. VCAM-1 only changed in old females stimulated with ISO 160. Our results highlight the relevance of considering and comparing in the same study females and aged organisms to improve the accuracy of applications to clinical studies.

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“…53 We recently published that although total NOS enzymatic activity was comparable among 12-week-old male and female SHRs and WKY, male SHRs have greater aortic NOS3 protein expression than male WKY with no strain differences in females. 54 Whereas WKY are often used as normotensive controls for SHRs, they are not a genetic match. For this reason, the current studies employed a pharmacological approach to lower BP in SHRs and remove genetic background as a variable.…”

Section: Discussionmentioning

confidence: 99%

Blood Pressure, Sex, and Female Sex Hormones Influence Renal Inner Medullary Nitric Oxide Synthase Activity and Expression in Spontaneously Hypertensive Rats

Sasser

Brinson

Tipton

et al. 2015

JAHA

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BackgroundWe previously reported that sexually mature female spontaneously hypertensive rats (SHRs) have greater nitric oxide (NO) synthase (NOS) enzymatic activity in the renal inner medulla (IM), compared to age‐matched males. However, the mechanisms responsible for this sexual dimorphism are unknown. The current study tested the hypothesis that sex differences in renal IM NOS activity and NOS1 expression in adult SHRs develop with sexual maturation and increases in blood pressure (BP) in a female sex hormone‐dependent manner.Methods and ResultsRenal IM were isolated from sexually immature 5‐week‐old and sexually mature 13‐week‐old male and female SHRs. Whereas NOS activity and NOS1 expression were comparable in 5‐ and 13‐week‐old male SHRs and 5‐week‐old female SHRs, 13‐week‐old females had greater NOS activity and NOS1 expression, compared to 5‐week‐old female SHRs and age‐matched males. NOS3 expression was greater in 5‐week‐old than 13‐week‐old SHRs regardless of sex. Treatment with antihypertensive therapy (hydrochlorothiazide and reserpine) from 6 to 12 weeks of age to attenuate age‐related increases in BP abolished the sex difference in NOS activity and NOS1 expression between sexually mature SHR males and females. To assess the role of female sex hormones in age‐related increases in NOS, additional females were ovariectomized (OVX), and NOS activity was studied 8 weeks post‐OVX. OVX decreased NOS activity and NOS1 expression.ConclusionsThe sex difference in renal IM NOS in SHR is mediated by a sex hormone‐ and BP‐dependent increase in NOS1 expression and NOS activity exclusively in females.

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Sex-specific alterations in NOS regulation of vascular function in aorta and mesenteric arteries from spontaneously hypertensive rats compared to Wistar Kyoto rats

Cited by 28 publications

References 55 publications

Sympathetic denervation facilitates L-type Ca2+ channel activation in renal but not in mesenteric resistance arteries

Sympathetic denervation facilitates L-type Ca2+ channel activation in renal but not in mesenteric resistance arteries

Age-, Gender-, and in Vivo Different Doses of Isoproterenol Modify in Vitro Aortic Vasoreactivity and Circulating VCAM-1

Blood Pressure, Sex, and Female Sex Hormones Influence Renal Inner Medullary Nitric Oxide Synthase Activity and Expression in Spontaneously Hypertensive Rats

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