Title

Angiotensin-II type 1 receptor-mediated hypertension in D4 dopamine receptor-deficient mice

Document Type

Journal Article

Publication Date

2-1-2006

Journal

Hypertension

Volume

47

Issue

2

DOI

10.1161/01.HYP.0000198427.96225.36

Keywords

Angiotensin II; Dopamine; Endothelin; Hypertension; Mice; Receptors, angiotensin II; Vasopressins

Abstract

Dopamine receptors are important in systemic blood pressure regulation. D4 receptors are expressed in the kidney and brain, but their role in cardiovascular regulation is unknown. In pentobarbital-anesthetized mice, systolic and diastolic blood pressures were elevated in sixth-generation D 4 receptor-deficient (D4-/-) mice and in tenth-generation D4-/- mice compared with D4 wild-type (D4+/+) littermates. The conscious blood pressures measured via a chronic arterial (femoral) catheter or telemetry (carotid) were also higher in D4-/- mice than in D 4 littermates. Basal renal and plasma renin concentrations were similar in the 2 mouse strains. The protein expression of angiotensin II type 1 receptor was increased in homogenates of kidney (330±53%, n=5) and brain (272±69%, n=5) of D4-/- mice relative to D 4+/+ mice (kidney: 100±12%, n=5; brain: 100±32%, n=5). The expression of the receptor in renal membrane was also increased in D4-/- mice (289±28%, n=8) relative to D4+/+ mice (100±14%, n=10). In contrast, the expression in the heart was similar in the 2 strains. Bolus intravenous injection of angiotensin II type 1 receptor antagonist losartan initially decreased mean arterial pressures to a similar degree in D4-/-and D4+/+ littermates. However, the hypotensive effect of losartan dissipated after 10 minutes in D4+/+ mice, whereas the effect persisted for >45 minutes in D 4-/- mice. We conclude that the absence of the D 4 receptor increases blood pressure, possibly via increased angiotensin II type 1 receptor expression. © 2006 American Heart Association, Inc.

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