Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice

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

    Research output: Contribution to journalArticle

    57 Scopus citations

    Abstract

    Polymorphism of the dopamine receptor type-2 (D2) gene is associated with essential hypertension. To assess whether D2 receptors participate in regulation of blood pressure (BP), we studied mice in which the D2 receptor was disrupted. In anesthetized mice, systolic and diastolic BPs (in millimeters of mercury) were higher in D2 homozygous and heterozygous mutant mice than in D2+/+ littermates. BP after α-adrenergic blockade decreased to a greater extent in D2-/- mice than in D2+/+ mice. Epinephrine excretion was greater in D2-/- mice than in D2+/+ mice, and acute adrenalectomy decreased BP to a similar level in D2-/- and D2+/+ mice. An endothelin B (ET[B]) receptor blocker for both ET(B1) and ET(B2) receptors decreased, whereas a selective ET(B1) blocker increased, BP in D2-/- mice but not D2+/+ mice. ET(B) receptor expression was greater in D2-/- mice than in D2+/+ mice. In contrast, blockade of ET(A) and V1 vasopressin receptors had no effect on BP in either D2-/- or D2+/+ mice. The hypotensive effect of an AT1 antagonist was also similar in D2-/- and D2+/+ mice. Basal Na+,K+-ATPase activities in renal cortex and medulla were higher in D2+/+ mice than in D2-/- mice. Urine flow and sodium excretion were higher in D2-/- mice than in D2+/+ mice before and after acute saline loading. Thus, complete loss of the D2 receptor results in hypertension that is not due to impairment of sodium excretion. Instead, enhanced vascular reactivity in the D2 mutant mice may be caused by increased sympathetic and ET(B) receptor activities.

    Original languageEnglish (US)
    Pages (from-to)303-308
    Number of pages6
    JournalHypertension
    Volume38
    Issue number3
    StatePublished - Dec 1 2001

    Keywords

    • Dopamine
    • Kidney
    • Na,K transporting ATPase
    • Receptors, dopamine
    • Receptors, endothelin

    ASJC Scopus subject areas

    • Internal Medicine

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  • Cite this

    Xiao, X. L., Bek, M., Asico, L. D., Yang, Z., Grandy, D. K., Goldstein, D. S., Rubinstein, M., Eisner, G. M., & Jose, P. A. (2001). Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice. Hypertension, 38(3), 303-308.