PMID:11566895

Citation	Li, XX, Bek, M, Asico, LD, Yang, Z, Grandy, DK, Goldstein, DS, Rubinstein, M, Eisner, GM and Jose, PA (2001) Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice. Hypertension 38:303-8
Abstract	Polymorphism of the dopamine receptor type-2 (D(2)) gene is associated with essential hypertension. To assess whether D(2) receptors participate in regulation of blood pressure (BP), we studied mice in which the D(2) receptor was disrupted. In anesthetized mice, systolic and diastolic BPs (in millimeters of mercury) were higher in D(2) homozygous and heterozygous mutant mice than in D(2)+/+ littermates. BP after alpha-adrenergic blockade decreased to a greater extent in D(2)-/- mice than in D(2)+/+ mice. Epinephrine excretion was greater in D(2)-/- mice than in D(2)+/+ mice, and acute adrenalectomy decreased BP to a similar level in D(2)-/- and D(2)+/+ 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 D(2)-/- mice but not D(2)+/+ mice. ET(B) receptor expression was greater in D(2)-/- mice than in D(2)+/+ mice. In contrast, blockade of ET(A) and V(1) vasopressin receptors had no effect on BP in either D(2)-/- or D(2)+/+ mice. The hypotensive effect of an AT(1) antagonist was also similar in D(2)-/- and D(2)+/+ mice. Basal Na(+),K(+)-ATPase activities in renal cortex and medulla were higher in D(2)+/+ mice than in D(2)-/- mice. Urine flow and sodium excretion were higher in D(2)-/- mice than in D(2)+/+ mice before and after acute saline loading. Thus, complete loss of the D(2) receptor results in hypertension that is not due to impairment of sodium excretion. Instead, enhanced vascular reactivity in the D(2) mutant mice may be caused by increased sympathetic and ET(B) receptor activities.
Links	PubMed
Keywords	Adrenergic alpha-Antagonists/pharmacology; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents/pharmacology; Blood Pressure/drug effects; Body Weight; Catechols/urine; Endothelin-1/pharmacology; Female; Genotype; Hypertension/drug therapy; Hypertension/genetics; Hypertension/physiopathology; Losartan/pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Oligopeptides/pharmacology; Phentolamine/pharmacology; Piperidines/pharmacology; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Adrenergic/drug effects; Receptors, Adrenergic/physiology; Receptors, Dopamine D2/genetics; Receptors, Dopamine D2/physiology; Receptors, Endothelin/agonists; Receptors, Endothelin/antagonists & inhibitors; Receptors, Endothelin/physiology; Receptors, Vasopressin/antagonists & inhibitors; Sodium/urine; Sodium-Potassium-Exchanging ATPase/metabolism; Urodynamics; Viper Venoms/pharmacology
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