Sex-related differences in nitric oxide content in healthy and hypertensive rats at rest and under stress conditions

Glushkovskaya-Semyachkina, O.; Anishchenko, T. G.; Sindyakova, T.; Leksina, O. V.; Berdnikova, V. A.

doi:10.1007/s10517-006-0277-y

Cited by 18 publications

(26 citation statements)

References 11 publications

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“…Experimental and epidemiological studies have reported blunted NO production in males relative to females (13,16,29). The results of this study provide mechanistic support for the hypothesis that renal NO levels are lower in male SHR compared with females.…”

Section: Discussionsupporting

confidence: 78%

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Renal NOS activity, expression, and localization in male and female spontaneously hypertensive rats

Sullivan

Pardieck

Hyndman

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Sullivan JC, Pardieck JL, Hyndman KA, Pollock JS. Renal NOS activity, expression, and localization in male and female spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 298: R61-R69, 2010. First published November 4, 2009 doi:10.1152/ajpregu.00526.2009.-The goal of this study was to examine the status of the renal nitric oxide (NO) system by determining NO synthase (NOS) isoform activity and expression within the three regions of the kidney in 14-wk-old male and female spontaneously hypertensive rats (SHR). NOS activity, and NOS1 and NOS3 protein expressions and localization were comparable in the renal cortex and outer medulla of male and female SHR. In contrast, male SHR had significantly less NOS1 and NOS3 enzymatic activity (0 Ϯ 5 and 53 Ϯ 7 pmol ⅐ mg Ϫ1 ⅐ 30 min Ϫ1 , respectively) compared with female SHR (37 Ϯ 16 and 172 Ϯ 40 pmol ⅐ mg Ϫ1 ⅐ 30 min Ϫ1 , respectively). Lower levels of inner medullary NOS1 activity in male SHR were associated with less NOS1 protein expression [45 Ϯ 7 relative densitometric units (RDU)] and fewer NOS1-positive cells in the renal inner medulla compared with female SHR (79 Ϯ 12 RDU). Phosphorylation of NOS3 is an important determinant of NOS activity. Male SHR had significantly greater phosphorylation of NOS3 on threonine 495 in the renal cortex compared with females (0.25 Ϯ 0.05 vs. 0.15 Ϯ 0.06 RDU). NOS3 phosphorylation was comparable in males and females in the other regions of the kidney. cGMP levels were measured as an indirect index of NO production. cGMP levels were significantly lower in the renal cortex (0.08 Ϯ 0.01 pmol/mg) and inner medulla (0.43 Ϯ 0.02 pmol/mg) of male SHR compared with females (cortex: 0.14 Ϯ 0.02 pmol/mg; inner medulla: 0.56 Ϯ 0.02 pmol/mg). Our data suggest that the effect of the sex of the animal on NOS activity and expression is different in the three regions of the SHR kidney and supports the hypothesis that male SHR have lower NO bioavailability compared with females. nitric oxide synthase; kidney; sex; gender; cGMP NITRIC OXIDE (NO) is an important regulator of blood pressure and kidney function (3,15,43). Therefore, it is not surprising that NO deficiencies have been linked with hypertension and the progression of chronic renal disease in both patients and experimental animals (2, 3, 45). All three NO synthase (NOS) isoforms have been localized to the kidney (1), and intrarenal inhibition of NOS has been shown to increase blood pressure (32). NOS1 (neuronal NOS) is predominantly localized in the macula densa, neurons, Bowman's capsule, and collecting duct, where it participates in the control of glomerular hemodynamics, renin release, and sodium excretion (1,24,46). Expression of NOS2 (inducible NOS) protein has been difficult to reproducibly detect in the normal kidney; however, there appears to be NOS2 mRNA in the medullary thick ascending limb (34). NOS3 (endothelial NOS) is localized in vascular endothelial cells and tubules, where it is important in the maintenance of glomerular filtration rate, vascular tone, and...

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Section: Discussionsupporting

confidence: 78%

“…Whole body NO levels have been reported to be greater in females compared with males (13,16,29,36), and a sex difference in the NO pathway may contribute to sexual dimorphisms in cardiovascular and renal pathologies. Under normotensive conditions female rats have been shown to have greater renal NOS1 immunoreactivity and NOS3 protein expression (22,36,40,55).…”

mentioning

confidence: 99%

Renal NOS activity, expression, and localization in male and female spontaneously hypertensive rats

Sullivan

Pardieck

Hyndman

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…These data are consistent with the results of our previous studies showing that the development of hypertension is accompanied by reduction of NO generation [1]. Indomethacin injection was followed by the pressor infl uences, whose amplitude did not differ in animals of two experimental groups (17-22 and 19-23%, respectively; p<0.05).…”

Section: Resultssupporting

confidence: 92%

“…Therefore, androgens have a stimulatory effect on functional activity of K ATP channels, which is reduced during hypertension. The stimulatory effects of testosterone on K ATP channels were observed in in vitro experiments on large vessels (e.g., aorta) [1] and in in vivo studies on coronary arteries [6].…”

Section: Resultsmentioning

confidence: 92%

Mechanisms for Vascular Effects of Androgens in Normotensive and Hypertensive Rats

Semyachkina-Glushkovskaya

Anishchenko

Кузнецова

et al. 2012

Bull Exp Biol Med

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Castration had no effect on baseline BP and vascular sensitivity to acetylcholine and deficiency of nitric oxide and prostacyclin in normotensive specimens. Castration of hypertensive specimens decreased BP and potentiated the hypotensive effects of acetylcholine, but did not modulate vascular sensitivity to the blockade of nitric oxide and prostacyclin synthesis. The removal of the testicles abolished the pressor influence of glybenclamide in hypertensive and, particularly, in normotensive males. These data indicate that the non-endothelial vascular effects of androgens (i.e., stimulation of K(ATP) channels) predominate under normal conditions. The activating effects of androgens on K(ATP) channels decrease during hypertension, which is accompanied by inhibition of endothelium-dependent vasorelaxation. The production of nitric oxide and prostacyclin remains unchanged under these conditions. Our results suggest that endothelium-derived hyperpolarizing factor is involved in these processes.

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“…In addition, females are characterized by cyclic changes in ovarian function associated with the development of follicles, ovulation, and corpora lutea formation. Variations of the hormonal profile during different phases of the estrous cycle modulate the course of stress reaction and processes in the hemostasis system [4].…”

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confidence: 99%

Sex-specific differences in changes of disturbed functional activity of platelets in albino rats under the effect of terahertz electromagnetic radiation at nitric oxide frequencies

et al. 2008

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The impact of electromagnetic oscillations of the terahertz band at frequencies of NO radiation and absorption molecular spectrum (150.176-150.664 GHz) for the functional activity of platelets was studied in albino rats exposed to immobilization stress. The effect of these waves was sex-specific: females were more sensitive to radiation than males. Relationship between the terahertz waves and phase of estrous cycle in females was detected: estrus females exhibited maximum sensitivity to these waves.

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Sex-related differences in nitric oxide content in healthy and hypertensive rats at rest and under stress conditions

Cited by 18 publications

References 11 publications

Renal NOS activity, expression, and localization in male and female spontaneously hypertensive rats

Renal NOS activity, expression, and localization in male and female spontaneously hypertensive rats

Mechanisms for Vascular Effects of Androgens in Normotensive and Hypertensive Rats

Sex-specific differences in changes of disturbed functional activity of platelets in albino rats under the effect of terahertz electromagnetic radiation at nitric oxide frequencies

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