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


CONCLUSIONS
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.
Li
Xiaoxil
X
The First Affiliated Hospital, Sun Yat-sen University of Medical Sciences, Guangzhou 510080, China.
Bek
Martin
M
Asico
Laureano D
LD
Yang
Zhiwei
Z
Rubinstein
Marcelo
M
Grandy
David K
DK
Goldstein
David S
DS
Eisner
Gilbert M
GM
Jose
Pedro A
PA
D000818:Animals; D017353:Gene Deletion; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044023:Receptor, Endothelin B; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000172:deficiency* / Q000235:genetics; D017466:Receptors, Endothelin / Q000378:metabolism*
D044023:Receptor, Endothelin B; D011943:Receptors, Adrenergic, beta; D017448:Receptors, Dopamine D2; D017466:Receptors, Endothelin