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 Grandy, David S. Goldstein, Marcelo Rubinstein, Gilbert M. Eisner, Pedro A. Jose

Research output: Contribution to journalArticle

55 Citations (Scopus)

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 - 2001
Externally publishedYes

Fingerprint

Endothelin B Receptors
Dopamine Receptors
Knockout Mice
Adrenergic Agents
Hypertension
Blood Pressure
Vasopressin Receptors
Sodium

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine

Cite this

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

Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice. / Xiao, Xi Li; Bek, Martin; Asico, Laureano D.; Yang, Zhiwei; Grandy, David; Goldstein, David S.; Rubinstein, Marcelo; Eisner, Gilbert M.; Jose, Pedro A.

In: Hypertension, Vol. 38, No. 3, 2001, p. 303-308.

Research output: Contribution to journalArticle

Xiao, XL, Bek, M, Asico, LD, Yang, Z, Grandy, D, Goldstein, DS, Rubinstein, M, Eisner, GM & Jose, PA 2001, 'Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice', Hypertension, vol. 38, no. 3, pp. 303-308.
Xiao XL, Bek M, Asico LD, Yang Z, Grandy D, Goldstein DS et al. Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice. Hypertension. 2001;38(3):303-308.
Xiao, Xi Li ; Bek, Martin ; Asico, Laureano D. ; Yang, Zhiwei ; Grandy, David ; Goldstein, David S. ; Rubinstein, Marcelo ; Eisner, Gilbert M. ; Jose, Pedro A. / Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice. In: Hypertension. 2001 ; Vol. 38, No. 3. pp. 303-308.
@article{f0b04be27c024d1b9d06ec97d15e5316,
title = "Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice",
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.",
keywords = "Dopamine, Kidney, Na,K transporting ATPase, Receptors, dopamine, Receptors, endothelin",
author = "Xiao, {Xi Li} and Martin Bek and Asico, {Laureano D.} and Zhiwei Yang and David Grandy and Goldstein, {David S.} and Marcelo Rubinstein and Eisner, {Gilbert M.} and Jose, {Pedro A.}",
year = "2001",
language = "English (US)",
volume = "38",
pages = "303--308",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice

AU - Xiao, Xi Li

AU - Bek, Martin

AU - Asico, Laureano D.

AU - Yang, Zhiwei

AU - Grandy, David

AU - Goldstein, David S.

AU - Rubinstein, Marcelo

AU - Eisner, Gilbert M.

AU - Jose, Pedro A.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Dopamine

KW - Kidney

KW - Na,K transporting ATPase

KW - Receptors, dopamine

KW - Receptors, endothelin

UR - http://www.scopus.com/inward/record.url?scp=0035572852&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035572852&partnerID=8YFLogxK

M3 - Article

VL - 38

SP - 303

EP - 308

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 3

ER -