Journal
HYPERTENSION
Volume 47, Issue 2, Pages 288-295Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.HYP.0000198427.96225.36
Keywords
dopamine; receptors, angiotensin II; mice; hypertension; angiotensin II; endothelin; vasopressins
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Funding
- NHLBI NIH HHS [HL23081, HL68696, HL074940] Funding Source: Medline
- NIDA NIH HHS [DA12062] Funding Source: Medline
- NIDDK NIH HHS [DK39308, DK52612] Funding Source: Medline
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Dopamine receptors are important in systemic blood pressure regulation. D-4 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 (D-4(-/-)) mice and in tenth-generation D-4(-/-) mice compared with D-4 wild-type (D-4(+/+)) littermates. The conscious blood pressures measured via a chronic arterial ( femoral) catheter or telemetry ( carotid) were also higher in D-4(-/-) mice than in D4 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 D-4(-/-) 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 D-4(-/-) mice (289 +/- 28%, n = 8) relative to D-4(+/)+ 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 D-4(-/-) and D-4(+/+) littermates. However, the hypotensive effect of losartan dissipated after 10 minutes in D-4(+/+) 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.
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