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

被引:57
作者
Bek, MJ
Wang, XY
Asico, LD
Jones, JE
Zheng, SP
Li, XX
Eisner, GM
Grandy, DK
Carey, RM
Soares-da-Silva, P
Jose, PA
机构
[1] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20057 USA
[2] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20057 USA
[3] Univ Clin Muenster, Dept Med, Munster, Germany
[4] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR USA
[5] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA
[6] Fac Med Porto, Inst Pharmacol & Therapeut, Oporto, Portugal
关键词
dopamine; receptors; angiotensin II; mice; hypertension; endothelin; vasopressins;
D O I
10.1161/01.HYP.0000198427.96225.36
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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.
引用
收藏
页码:288 / 295
页数:8
相关论文
共 55 条
[1]   Role of the D-1A dopamine receptor in the pathogenesis of genetic hypertension [J].
Albrecht, FE ;
Drago, J ;
Felder, RA ;
Printz, MP ;
Eisner, GM ;
Robillard, JE ;
Sibley, DR ;
Westphal, HJ ;
Jose, PA .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (10) :2283-2288
[2]   Localization of dopamine receptor subtypes in systemic arteries [J].
Amenta, F ;
Barili, P ;
Bronzetti, E ;
Felici, L ;
Mignini, F ;
Ricci, A .
CLINICAL AND EXPERIMENTAL HYPERTENSION, 2000, 22 (03) :277-288
[3]   Cellular distribution of the rat D-4 dopamine receptor protein in the CNS using anti-receptor antisera [J].
Ariano, MA ;
Wang, J ;
Noblett, KL ;
Larson, ER ;
Sibley, DR .
BRAIN RESEARCH, 1997, 752 (1-2) :26-34
[4]   Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension [J].
Asico, LD ;
Ladines, C ;
Fuchs, S ;
Accili, D ;
Carey, RM ;
Semeraro, C ;
Pocchiari, F ;
Felder, RA ;
Eisner, GM ;
Jose, PA .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (03) :493-498
[5]   HORMONAL-SYMPATHETIC INTERACTIONS IN LONG-TERM REGULATION OF ARTERIAL-PRESSURE - AN HYPOTHESIS [J].
BROOKS, VL ;
OSBORN, JW .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1995, 268 (06) :R1343-R1358
[6]  
CAREY RM, 1986, RECENT PROG HORM RES, V42, P251
[7]   Update on the role of the AT2 receptor [J].
Carey, RM .
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION, 2005, 14 (01) :67-71
[8]   Distribution of D4 dopamine receptor in rat brain with sequence-specific antibodies [J].
Defagot, MC ;
Malchiodi, EL ;
Villar, MJ ;
Antonelli, MC .
MOLECULAR BRAIN RESEARCH, 1997, 45 (01) :1-12
[9]   NEUROGENIC ACTIONS OF ANGIOTENSIN-II [J].
FERRARIO, CM .
HYPERTENSION, 1983, 5 (06) :V73-V79
[10]   Long-term sympatho-excitatory effect of angiotensin II: A mechanism of spontaneous and renovascular hypertension [J].
Fink, GD .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 1997, 24 (01) :91-95