Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SS × BN cross

Kunert, Mary Pat; Dwinell, Melinda R.; Drenjančević-Perić, Ines; Lombard, Julian H.

doi:10.1152/ajpregu.00038.2008

Cited by 12 publications

(22 citation statements)

References 68 publications

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“…The segments were washed with 20 ml fresh KS (37°C) at 10-min intervals for 30 min until they reverted to resting tension. The maximal contraction response (MR) was then obtained by adding 0.1 mM norepinephrine (NE; Sigma) in 80 mM KCl to the chamber as previously described (23). Following a washout period of 90 min, the concentration-response relationship to PE (1 nM-0.1 mM) and vasorelaxing-response relationship to atrial natriuretic peptide (ANP, 0.3 nM-M) were examined and analyzed.…”

Section: Vascular Reactivity Measurementsmentioning

confidence: 99%

Physiological roles of endogenous ouabain in normal rats

Nesher¹,

Dvela²,

Igbokwe

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Endogenous ouabain (EO)-like compounds are synthesized in and released from the adrenal gland. Although EO has been implicated in several pathological states such as hypertension and heart and kidney failure, its physiological roles in normal animal have not been elucidated. To address this issue, we studied the effects of reduction in plasma EO resulting from antiouabain antibody administration. Normal rats were treated for 28 days with antiouabain antibodies or rabbit IgG as control. Infusions were delivered through a jugular vein cannula by osmotic pumps, and blood pressure was monitored by tail-cuff plethysmography. The animals were housed in metabolic cages to measure water and food consumption and urine excretion. After 28 days, the thoracic aorta was isolated and used to study phenylephrine-induced contraction and atrial natriuretic peptide (ANP)-induced vasorelaxation. The adrenal gland cortex was enlarged in the antiouabain antibody-treated rats. Moreover, on the second day of treatment, there was a significant transient reduction in natriuresis in the antiouabain antibody-treated rats, suggesting that EO is a natriuretic hormone. Reduction in natriuresis was also observed when EO levels were reduced by active immunization resulting from sequential injection of ouabain-albumin. Furthermore, following 28 days of treatment, the response to phenylephrine was significantly lowered and that to ANP was significantly increased in aortic rings from antiouabain antibodytreated rats. These findings show for the first time that circulatory ouabain plausibly originating in the adrenal has physiological roles controlling vasculature tone and sodium homeostasis in normal rats.

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Section: Vascular Reactivity Measurementsmentioning

confidence: 99%

Physiological roles of endogenous ouabain in normal rats

Nesher¹,

Dvela²,

Igbokwe

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Lower incidence of cardiovascular disease in premenopausal women, relative to age-matched men, implicates a significant role for female gonadal hormones in the beneficial effects on cardiovascular function. A large body of clinical and basic research has also documented sex-specific differences in offspring with high blood pressure and endothelial dysfunction, due to a variety of stresses experienced by pregnant mothers (15,22,36). This phenomenon, fetal programming of hypertension/endothelial dysfunction, is obviously not mediated by the gonadal hormones and implicates that the sex genome can contribute to the development of vascular sex-related differences in the mother's uterus.…”

mentioning

confidence: 99%

Intrinsic sex-specific differences in microvascular endothelial cell phosphodiesterases

Wang

Bingaman

Huxley

2010

American Journal of Physiology-Heart and Circulatory Physiology

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The importance of gonadal hormones in the regulation of vascular function has been documented. An alternate and essential contribution of the sex chromosomes to sex differences in vascular function is poorly understood. We reported previously sex differences in microvessel permeability (P(s)) responses to adenosine that were mediated by the cAMP signaling pathway (Wang J, PhD thesis, 2005; Wang J and Huxley V, Proceedings of the VIII World Congress of Microcirculation, 2007; Wang J and Huxley VH, Am J Physiol Heart Circ Physiol 291: H3094-H3105, 2006). The two cyclic nucleotides, cAMP and cGMP, central to the regulation of vascular barrier integrity, are hydrolyzed by phosphodiesterases (PDE). We hypothesized that microvascular endothelial cells (EC) would retain intrinsic and inheritable sexually dimorphic genes with respect to the PDEs modulating EC barrier function. Primary cultured microvascular EC from skeletal muscles isolated from male and female rats, respectively, were used. SRY (a sex-determining region Y gene) mRNA expression was observed exclusively in male, not female, cells. The predominant isoform among PDE1-5, present in both XY and XX EC, was PDE4. Expression mRNA levels of PDE1A (male > female) and PDE3B (male < female) were sex dependent; PDE2A, PDE4D, and PDE5A were sex independent. Barrier function, P(s), was determined from measures of albumin flux across confluent primary cultured microvessel XY and XX EC monolayers. Consistent with intact in situ microvessels, basal monolayer P(s) did not differ between XY (1.7 +/- 0.2 x 10(-6) cm/s; n = 8) and XX (1.8 +/- 0.1 x 10(-6) cm/s; n = 10) EC. Cilostazol, a PDE3 inhibitor, reduced (11%, P < 0.05) P(s) in XX, not XY, cells. These findings demonstrate the presence and maintenance of intrinsic sex-related differences in gene expression and cellular phenotype by microvascular EC in a gonadal-hormone-free environment. Furthermore, intrinsic cell-sex likely contributes significantly to sexual dimorphism in cardiovascular function.

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“…Vessel integrity was gauged with a challenge of 10 M phenylephrine (PE), followed by 10 M acetylcholine (ACh). Arteries that failed to contract more than 4 mN past baseline and/or relax more than 40% from maximal contraction were excluded from further analysis (23). Following the integrity challenge, the myograph baths were washed with PSS three times, and the baseline level was reestablished.…”

Section: Generation Of Ssmentioning

confidence: 99%

Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12

Prisco

Priestley

Weinberg

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12. Am J Physiol Heart Circ Physiol 307: H1103-H1110, 2014. First published August 22, 2014; doi:10.1152/ajpheart.00464.2014.-We previously isolated a 6.1-Mb region of SS/Mcwi (Dahl salt-sensitive) rat chromosome 12 (13.4 -19.5 Mb) that significantly elevated blood pressure (BP) (⌬ϩ34 mmHg, P Ͻ 0.001) compared with the SS-12 BN consomic control. In the present study, we examined the role of vascular dysfunction and remodeling in hypertension risk associated with the 6.1-Mb (13.4 -19.5 Mb) locus on rat chromosome 12 by reducing dietary salt, which lowered BP levels so that there were no substantial differences in BP between strains. Consequently, any observed differences in the vasculature were considered BP-independent. We also reduced the candidate region from 6.1 Mb with 133 genes to 2 Mb with 23 genes by congenic mapping. Both the 2 Mb and 6.1 Mb congenic intervals were associated with hypercontractility and decreased elasticity of resistance vasculature prior to elevations of BP, suggesting that the vascular remodeling and dysfunction likely contribute to the pathogenesis of hypertension in these congenic models. Of the 23 genes within the narrowed congenic interval, 12 were differentially expressed between the resistance vasculature of the 2 Mb congenic and SS-12 BN consomic strains. Among these, Grifin was consistently upregulated 2.7 Ϯ 0.6-fold (P Ͻ 0.05) and 2.0 Ϯ 0.3-fold (P Ͻ 0.01), and Chst12 was consistently downregulated Ϫ2.8 Ϯ 0.3-fold (P Ͻ 0.01) and Ϫ4.4 Ϯ 0.4-fold (P Ͻ 0.00001) in the 2 Mb congenic compared with SS-12 BN consomic under normotensive and hypertensive conditions, respectively. A syntenic region on human chromosome 7 has also been associated with BP regulation, suggesting that identification of the genetic mechanism(s) underlying cardiovascular phenotypes in this congenic strain will likely be translated to a better understanding of human hypertension.

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Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SS × BN cross

Cited by 12 publications

References 68 publications

Physiological roles of endogenous ouabain in normal rats

Physiological roles of endogenous ouabain in normal rats

Intrinsic sex-specific differences in microvascular endothelial cell phosphodiesterases

Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12

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