Vascular reactivity of mesenteric arteries and veins to endothelin-1 in a murine model of high blood pressure

Pérez-Rivera, Alex A.; Fink, Gregory D.; Galligan, James J.

doi:10.1016/j.vph.2005.02.014

Cited by 18 publications

(19 citation statements)

References 29 publications

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“…Another possibility is that the cavernosal tissue displays a differential sensitivity to the effects of ET-1 or ET A receptor blockade, in contrast to that of other vascular beds. As an example, differential regulation of ET-1 contractile mechanisms has been demonstrated between murine mesenteric arteries and veins (Pérez-Rivera et al 2005). Another possible explanation is that the cavernosal ET-1 system in mice is less susceptible to the effects of mineralocorticoid hypertension.…”

Section: Discussionmentioning

confidence: 99%

DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosumThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

Carneiro

Giachini

Lima

et al. 2008

Can. J. Physiol. Pharmacol.

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The penis is kept in the flaccid state mainly via a tonic activity of norepinephrine and endothelins (ETs). ET-1 is important in salt-sensitive forms of hypertension. We hypothesized that cavernosal responses to ET-1 are enhanced in deoxycorticosterone acetate (DOCA)-salt mice and that blockade 1 This article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.2Corresponding author (e-mail: E-mail: fcarneiro@mcg.edu). NIH Public Access

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Section: Discussionmentioning

confidence: 99%

DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosumThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

Carneiro

Giachini

Lima

et al. 2008

Can. J. Physiol. Pharmacol.

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“…Tg-GCH mice of C57BL/6 background were bred in-house. DOCA-salt hypertension was created as described previously 10 (Data Supplement). BP was measured by both noninvasive tail-cuff and radiotelemetry methods.…”

Section: Doca-salt Hypertensive Micementioning

confidence: 99%

“…Seven to 10 days after implantation surgery, mice underwent DOCA-salt or sham surgery. 10 All animal procedures were in accordance with the institutional guidelines of the Michigan State University.…”

Section: Doca-salt Hypertensive Micementioning

confidence: 99%

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Endothelium-Specific GTP Cyclohydrolase I Overexpression Attenuates Blood Pressure Progression in Salt-Sensitive Low-Renin Hypertension

Guan

Nicholas

et al. 2008

Circulation

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Background-Tetrahydrobiopterin (BH4) is an essential cofactor of endothelial nitric oxide synthase (eNOS). When BH4 levels are decreased, eNOS becomes uncoupled to produce superoxide anion (O 2 Ϫ ) instead of NO, which contributes to endothelial dysfunction. Deoxycorticosterone acetate (DOCA)-salt hypertension is characterized by a suppressed plasma renin level due to sodium retention but manifests in eNOS uncoupling; however, how endogenous BH4 regulates blood pressure is unknown. GTP cyclohydrolase I (GTPCH I) is the rate-limiting enzyme for de novo BH4 synthesis. This study tested the hypothesis that endothelium-specific GTPCH I overexpression retards the progression of hypertension through preservation of the structure and function of resistance mesenteric arteries. Methods and Results-During 3 weeks of DOCA-salt treatment, arterial blood pressure was increased significantly in wild-type mice, as determined by radiotelemetry, but this increase was attenuated in transgenic mice with endothelium-specific GTPCH I overexpression (Tg-GCH). Arterial GTPCH I activity and BH4 levels were decreased significantly in wild-type DOCA-salt mice, but both were preserved in Tg-GCH mice despite DOCA-salt treatment. Significant remodeling of resistance mesenteric arteries (Ϸ100-m outside diameter) in wild-type DOCA-salt mice exists, evidenced by increased medial cross-sectional area, media thickness, and media-lumen ratio and overexpression of tenascin C, an extracellular matrix glycoprotein that contributes to hypertrophic remodeling; all of these effects were prevented in DOCA-salt-treated Tg-GCH mice. Furthermore, NO-mediated relaxation in mesenteric arteries was significantly improved in DOCA-salt-treated Tg-GCH mice, in parallel with reduced O 2 Ϫ levels. Finally, phosphorylation of eNOS at serine residue 1177 (eNOS-S 1177 ), but not its dimer-monomer ratio, was decreased significantly in wild-type DOCA-salt mice compared with sham controls but was preserved in DOCA-salt-treated Tg-GCH mice.Conclusions-These results demonstrate that endothelium-specific GTPCH I overexpression abrogates O 2 Ϫ production and preserves eNOS phosphorylation, which results in preserved structural and functional integrity of resistance mesenteric arteries and lowered blood pressure in low-renin hypertension.

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“…Animals within the weight range used (25 -30g) received about 80 μL of the anesthetic. Standard surgical procedures were used to prepare DOCA-salt hypertensive mice (Perez-Rivera et al, 2005a;2005b). SHAM mice were unilaterally nephrectomized, but they received no DOCA pellet implantation and were given tap water.…”

Section: Preparation Of Doca-salt Hypertensive Animalsmentioning

confidence: 99%

Differential contributions of alpha-1 and alpha-2 adrenoceptors to vasoconstriction in mesenteric arteries and veins of normal and hypertensive mice

Pérez-Rivera¹,

Hlavacova²,

Rosario-Colón³

et al. 2007

Vascular Pharmacology

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Mesenteric veins are more sensitive than arteries to the constrictor effects of sympathetic nerve stimulation and α-adrenergic receptor agonists. In the present study, we tested the hypothesis that α 2 -adrenergic receptors (α 2 -ARs) contribute to in vitro agonist-induced constriction in veins but not arteries and that α 2 -AR function is down-regulated in mesenteric arteries and veins in deoxycorticosterone acetate-salt (DOCA-salt) hypertension. Norepinephrine (NE) concentrationresponse curves were similar in SHAM and DOCA-salt arteries and veins indicating that adrenergic reactivity of mesenteric blood vessels is not altered in murine DOCA-salt hypertension in vitro. Veins were 30-fold more sensitive to NE than arteries. The α 1 -AR antagonist, prazosin (. 003-0.3μM), produced concentration-dependent rightward shifts of the NE concentrationresponse curves in arteries but not veins. The α 2 -AR agonists, clonidine and UK-14,304, did not constrict arteries or veins in the absence or presence of indomethacin (10 μM) and nitro-Larginine (NLA; 100 μM). The α 2 -AR antagonists, yohimbine (.003-0.3 μM) and rauwolscine (0.1μM) did not affect NE responses in SHAM or DOCA-salt arteries but antagonized NE responses in veins. These data indicate that there are different α-AR contractile mechanisms in murine mesenteric arteries and veins. α 1 -ARs, but not α 2 -ARs, mediate direct contractile responses in arteries and veins while α 2 -ARs contribute indirectly to NE-induced constrictions in veins but not arteries in vitro. There may be direct protein-protein interactions between α 1 -and α 2 -ARs or between their signaling pathways in veins. This contribution of α 2 -ARs may account for the greater sensitivity of veins compared to arteries to the contractile effects of NE.

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Vascular reactivity of mesenteric arteries and veins to endothelin-1 in a murine model of high blood pressure

Cited by 18 publications

References 29 publications

DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosumThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosumThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

Endothelium-Specific GTP Cyclohydrolase I Overexpression Attenuates Blood Pressure Progression in Salt-Sensitive Low-Renin Hypertension

Differential contributions of alpha-1 and alpha-2 adrenoceptors to vasoconstriction in mesenteric arteries and veins of normal and hypertensive mice

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