Disruption of the D(2) dopamine receptor produces adrenergic and endothelin B receptor-dependent hypertension

Xiaoxil Li, Martin Bek, Laureano D. Asico, Zhiwei Yang, Marcelo Rubinstein, David K. Grandy, David S. Goldstein, Gilbert M. Eisner, Pedro A. Jose

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    Abstract

    OBJECTIVE: To assess whether D(2) receptors participate in the regulation of genetic hypertension. METHODS: Arterial pressure was measured in mice mutant for the D(2) dopamine receptors, and the interactions between D(2) dopamine receptors and other vasopressor systems were also studied. RESULTS: Both systolic blood pressure (BP) in D(2) mutant (D(2)-/-) and hybrid (D(2)+/-) mice (128 +/- 2 mm Hg, 129 +/- 4 mm Hg) and diastolic BP (107 +/- 2 mm Hg, 108 +/- 3 mm Hg) were higher than in wild-type (D(2)+/+) mice (104 +/- 2 mm Hg, 77 +/- 1 mm Hg). The BP after alpha-adrenergic blockade decreased to a greater extent in D(2)-/- than in D(2)+/+ mice. Epinephrine excretion was greater in D(2)-/- than in D(2)+/+ mice and adrenalectomy decreased blood pressure to a greater extent in D(2)-/- than in D(2)+/+ mice. The non specific endothelin B (ETB) blocker (BQ788) decreased BP in D(2)-/- but had not in D(2)+/+ mice. The ETB1 blocker RES 701 - 1 increased BP in D(2)-/- but not D(2)+/+ mice. ET-1 and the ETB agonist, sarafatoxin S6c increased BP to a greater extent in D(2)+/+ than in D(2)-/- mice. Circulating ET-like immunoreactive peptides were similar in D(2)-/- and D(2)+/+ mice but ETB receptor expression was greater in D(2)-/- than in D(2)+/+ mice. In contrast, blockade of ETA and V(1) vasopressin receptors had no effect on BP in either D(2)-/- and D(2)+/+ mice. The hypotensive effect of the AT(1) antagonist, losartan, was also similar in D(2)-/- and D(2)+/+ mice. The greater basal sodium excretion and lower renal Na(+)/K(+)ATPase activity in D(2)-/- than in D(2)+/+ mice indicate that sodium retention was not the cause of hypertension in these animals. CONCLUSION: Hypertension in the D(2) mutant mice may be caused by absent inhibitory effect of D(2) receptors on sympathetic outflow coupled with increased ETB2 activity.

    Original languageEnglish (US)
    Pages (from-to)703-707
    Number of pages5
    JournalZhonghua yi xue za zhi
    Volume82
    Issue number10
    StatePublished - May 25 2002

    ASJC Scopus subject areas

    • Medicine(all)

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    Li, X., Bek, M., Asico, L. D., Yang, Z., Rubinstein, M., Grandy, D. K., Goldstein, D. S., Eisner, G. M., & Jose, P. A. (2002). Disruption of the D(2) dopamine receptor produces adrenergic and endothelin B receptor-dependent hypertension. Zhonghua yi xue za zhi, 82(10), 703-707.