Aberrant D1 and D3 Dopamine Receptor Transregulation in Hypertension
ABSTRACT—Dopamine plays a role in the regulation of blood pressure by inhibition of sodium transport in renal proximal tubules (RPTs) and relaxation of vascular smooth muscles. Because dopamine receptors can regulate and interact with each other, we studied the interaction of D1 and D3 receptors in...
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| Veröffentlicht in: | Hypertension (Dallas, Tex. 1979) Tex. 1979), 2004-03, Vol.43 (3), p.654-660 |
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| container_title | Hypertension (Dallas, Tex. 1979) |
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| creator | Zeng, Chunyu Wang, Dan Asico, Laureano D Welch, William J Wilcox, Christopher S Hopfer, Ulrich Eisner, Gilbert M Felder, Robin A Jose, Pedro A |
| description | ABSTRACT—Dopamine plays a role in the regulation of blood pressure by inhibition of sodium transport in renal proximal tubules (RPTs) and relaxation of vascular smooth muscles. Because dopamine receptors can regulate and interact with each other, we studied the interaction of D1 and D3 receptors in immortalized RPT cells and mesenteric arteries from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs), and in human coronary artery smooth muscle cells (CASMCs). In WKY rats, the D1-like agonist, fenoldopam, increased D3 receptor protein in a time-dependent and concentration-dependent manner (EC50=4.5×10 M, t1/2=15.8 hours). In SHRs, fenoldopam (10 M) actually decreased the expression of D3 receptors. D1 and D3 receptor co-immunoprecipitation was increased by fenoldopam (10 M/24 h) in WKY rats but not in SHRs. The effects of fenoldopam in CASMCs were similar as those in WKY RPT cells (ie, fenoldopam increased D1 and D3 receptor proteins). Both D3 (PD128907, Emax=80%±6%, pED50=5±0.1) and D1-like receptor (fenoldopam, Emax=81%±8%, pED50=5±0.2, n=12) agonists relaxed mesenteric arterial rings. Co-stimulation of D1 and D3 receptors led to additive vasorelaxation in WKY rats, but not in SHRs. D1 and D3 receptors interact differently in WKY and SHRs. Altered interactions between D1 and D3 receptors may play a role in the pathogenesis of genetic hypertension, including human hypertension, because these receptors also interact in human vascular smooth muscle cells. |
| doi_str_mv | 10.1161/01.HYP.0000114601.30306.bf |
| format | Article |
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Because dopamine receptors can regulate and interact with each other, we studied the interaction of D1 and D3 receptors in immortalized RPT cells and mesenteric arteries from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs), and in human coronary artery smooth muscle cells (CASMCs). In WKY rats, the D1-like agonist, fenoldopam, increased D3 receptor protein in a time-dependent and concentration-dependent manner (EC50=4.5×10 M, t1/2=15.8 hours). In SHRs, fenoldopam (10 M) actually decreased the expression of D3 receptors. D1 and D3 receptor co-immunoprecipitation was increased by fenoldopam (10 M/24 h) in WKY rats but not in SHRs. The effects of fenoldopam in CASMCs were similar as those in WKY RPT cells (ie, fenoldopam increased D1 and D3 receptor proteins). Both D3 (PD128907, Emax=80%±6%, pED50=5±0.1) and D1-like receptor (fenoldopam, Emax=81%±8%, pED50=5±0.2, n=12) agonists relaxed mesenteric arterial rings. Co-stimulation of D1 and D3 receptors led to additive vasorelaxation in WKY rats, but not in SHRs. D1 and D3 receptors interact differently in WKY and SHRs. Altered interactions between D1 and D3 receptors may play a role in the pathogenesis of genetic hypertension, including human hypertension, because these receptors also interact in human vascular smooth muscle cells.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/01.HYP.0000114601.30306.bf</identifier><identifier>PMID: 14732731</identifier><identifier>CODEN: HPRTDN</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Animals ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cell Line ; Clinical manifestations. Epidemiology. Investigative techniques. Etiology ; Coronary Vessels - cytology ; Dopamine Agonists - pharmacology ; Fenoldopam - pharmacology ; Fundamental and applied biological sciences. Psychology ; Hemodynamics. Rheology ; Humans ; Hypertension - metabolism ; Hypertension - physiopathology ; Kidney Tubules, Proximal - drug effects ; Kidney Tubules, Proximal - metabolism ; Male ; Medical sciences ; Mesenteric Arteries - physiopathology ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - metabolism ; Precipitin Tests ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Receptors, Dopamine D1 - agonists ; Receptors, Dopamine D1 - metabolism ; Receptors, Dopamine D2 - agonists ; Receptors, Dopamine D2 - metabolism ; Receptors, Dopamine D3 ; Vasodilation ; Vertebrates: cardiovascular system</subject><ispartof>Hypertension (Dallas, Tex. 1979), 2004-03, Vol.43 (3), p.654-660</ispartof><rights>2004 American Heart Association, Inc.</rights><rights>2004 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Mar 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15544259$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14732731$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zeng, Chunyu</creatorcontrib><creatorcontrib>Wang, Dan</creatorcontrib><creatorcontrib>Asico, Laureano D</creatorcontrib><creatorcontrib>Welch, William J</creatorcontrib><creatorcontrib>Wilcox, Christopher S</creatorcontrib><creatorcontrib>Hopfer, Ulrich</creatorcontrib><creatorcontrib>Eisner, Gilbert M</creatorcontrib><creatorcontrib>Felder, Robin A</creatorcontrib><creatorcontrib>Jose, Pedro A</creatorcontrib><title>Aberrant D1 and D3 Dopamine Receptor Transregulation in Hypertension</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><description>ABSTRACT—Dopamine plays a role in the regulation of blood pressure by inhibition of sodium transport in renal proximal tubules (RPTs) and relaxation of vascular smooth muscles. Because dopamine receptors can regulate and interact with each other, we studied the interaction of D1 and D3 receptors in immortalized RPT cells and mesenteric arteries from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs), and in human coronary artery smooth muscle cells (CASMCs). In WKY rats, the D1-like agonist, fenoldopam, increased D3 receptor protein in a time-dependent and concentration-dependent manner (EC50=4.5×10 M, t1/2=15.8 hours). In SHRs, fenoldopam (10 M) actually decreased the expression of D3 receptors. D1 and D3 receptor co-immunoprecipitation was increased by fenoldopam (10 M/24 h) in WKY rats but not in SHRs. The effects of fenoldopam in CASMCs were similar as those in WKY RPT cells (ie, fenoldopam increased D1 and D3 receptor proteins). Both D3 (PD128907, Emax=80%±6%, pED50=5±0.1) and D1-like receptor (fenoldopam, Emax=81%±8%, pED50=5±0.2, n=12) agonists relaxed mesenteric arterial rings. Co-stimulation of D1 and D3 receptors led to additive vasorelaxation in WKY rats, but not in SHRs. D1 and D3 receptors interact differently in WKY and SHRs. Altered interactions between D1 and D3 receptors may play a role in the pathogenesis of genetic hypertension, including human hypertension, because these receptors also interact in human vascular smooth muscle cells.</description><subject>Animals</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cell Line</subject><subject>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</subject><subject>Coronary Vessels - cytology</subject><subject>Dopamine Agonists - pharmacology</subject><subject>Fenoldopam - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hemodynamics. Rheology</subject><subject>Humans</subject><subject>Hypertension - metabolism</subject><subject>Hypertension - physiopathology</subject><subject>Kidney Tubules, Proximal - drug effects</subject><subject>Kidney Tubules, Proximal - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mesenteric Arteries - physiopathology</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Precipitin Tests</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Rats, Inbred WKY</subject><subject>Receptors, Dopamine D1 - agonists</subject><subject>Receptors, Dopamine D1 - metabolism</subject><subject>Receptors, Dopamine D2 - agonists</subject><subject>Receptors, Dopamine D2 - metabolism</subject><subject>Receptors, Dopamine D3</subject><subject>Vasodilation</subject><subject>Vertebrates: cardiovascular system</subject><issn>0194-911X</issn><issn>1524-4563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0V9LwzAQAPAgis7pV5Ai6FtrLn_bR7HqBEGRCfpUku7qql1bk5bhtzfDiWDguDv4EY47Qk6BJgAKLigks9fHhIYHIFRoOeVUJbbaIROQTMRCKr5LJhQyEWcALwfk0Pv3wIUQep8cgNCcaQ4Tkl9adM60Q5RDZNpFlPMo73qzqluMnrDEfuhcNA_CO3wbGzPUXRvVbTT76tEN2PrQH5G9yjQej7d5Sp5vrudXs_j-4fbu6vI-XjIlZQyLVGeaKxCMMstLSLOKWdTa2lJlmDKlSkkzaxkaaSplmMJQl1VlU2NUyqfk_Off3nWfI_qhWNW-xKYxLXajLzQEpKkI8PQffO9G14bZCkYlS3mqNuhki0a7wkXRu3pl3Ffxu5wAzrbA-NI0VVhCWfs_J6UQTGbBiR-37poBnf9oxjW6YommGZbF5kyCqTRmIYc7URqHYJJ_A-QQg78</recordid><startdate>200403</startdate><enddate>200403</enddate><creator>Zeng, Chunyu</creator><creator>Wang, Dan</creator><creator>Asico, Laureano D</creator><creator>Welch, William J</creator><creator>Wilcox, Christopher S</creator><creator>Hopfer, Ulrich</creator><creator>Eisner, Gilbert M</creator><creator>Felder, Robin A</creator><creator>Jose, Pedro A</creator><general>American Heart Association, Inc</general><general>Lippincott</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>200403</creationdate><title>Aberrant D1 and D3 Dopamine Receptor Transregulation in Hypertension</title><author>Zeng, Chunyu ; Wang, Dan ; Asico, Laureano D ; Welch, William J ; Wilcox, Christopher S ; Hopfer, Ulrich ; Eisner, Gilbert M ; Felder, Robin A ; Jose, Pedro A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h2655-1d87973614202b3c189f2be77bbc69e8266c509bb2ea5af6a26eb2ecffb8aa683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cell Line</topic><topic>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</topic><topic>Coronary Vessels - cytology</topic><topic>Dopamine Agonists - pharmacology</topic><topic>Fenoldopam - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hemodynamics. Rheology</topic><topic>Humans</topic><topic>Hypertension - metabolism</topic><topic>Hypertension - physiopathology</topic><topic>Kidney Tubules, Proximal - drug effects</topic><topic>Kidney Tubules, Proximal - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mesenteric Arteries - physiopathology</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Precipitin Tests</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Rats, Inbred WKY</topic><topic>Receptors, Dopamine D1 - agonists</topic><topic>Receptors, Dopamine D1 - metabolism</topic><topic>Receptors, Dopamine D2 - agonists</topic><topic>Receptors, Dopamine D2 - metabolism</topic><topic>Receptors, Dopamine D3</topic><topic>Vasodilation</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zeng, Chunyu</creatorcontrib><creatorcontrib>Wang, Dan</creatorcontrib><creatorcontrib>Asico, Laureano D</creatorcontrib><creatorcontrib>Welch, William J</creatorcontrib><creatorcontrib>Wilcox, Christopher S</creatorcontrib><creatorcontrib>Hopfer, Ulrich</creatorcontrib><creatorcontrib>Eisner, Gilbert M</creatorcontrib><creatorcontrib>Felder, Robin A</creatorcontrib><creatorcontrib>Jose, Pedro A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zeng, Chunyu</au><au>Wang, Dan</au><au>Asico, Laureano D</au><au>Welch, William J</au><au>Wilcox, Christopher S</au><au>Hopfer, Ulrich</au><au>Eisner, Gilbert M</au><au>Felder, Robin A</au><au>Jose, Pedro A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant D1 and D3 Dopamine Receptor Transregulation in Hypertension</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>2004-03</date><risdate>2004</risdate><volume>43</volume><issue>3</issue><spage>654</spage><epage>660</epage><pages>654-660</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><coden>HPRTDN</coden><abstract>ABSTRACT—Dopamine plays a role in the regulation of blood pressure by inhibition of sodium transport in renal proximal tubules (RPTs) and relaxation of vascular smooth muscles. Because dopamine receptors can regulate and interact with each other, we studied the interaction of D1 and D3 receptors in immortalized RPT cells and mesenteric arteries from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs), and in human coronary artery smooth muscle cells (CASMCs). In WKY rats, the D1-like agonist, fenoldopam, increased D3 receptor protein in a time-dependent and concentration-dependent manner (EC50=4.5×10 M, t1/2=15.8 hours). In SHRs, fenoldopam (10 M) actually decreased the expression of D3 receptors. D1 and D3 receptor co-immunoprecipitation was increased by fenoldopam (10 M/24 h) in WKY rats but not in SHRs. The effects of fenoldopam in CASMCs were similar as those in WKY RPT cells (ie, fenoldopam increased D1 and D3 receptor proteins). Both D3 (PD128907, Emax=80%±6%, pED50=5±0.1) and D1-like receptor (fenoldopam, Emax=81%±8%, pED50=5±0.2, n=12) agonists relaxed mesenteric arterial rings. Co-stimulation of D1 and D3 receptors led to additive vasorelaxation in WKY rats, but not in SHRs. D1 and D3 receptors interact differently in WKY and SHRs. Altered interactions between D1 and D3 receptors may play a role in the pathogenesis of genetic hypertension, including human hypertension, because these receptors also interact in human vascular smooth muscle cells.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>14732731</pmid><doi>10.1161/01.HYP.0000114601.30306.bf</doi><tpages>7</tpages></addata></record> |
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| ispartof | Hypertension (Dallas, Tex. 1979), 2004-03, Vol.43 (3), p.654-660 |
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| subjects | Animals Arterial hypertension. Arterial hypotension Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cell Line Clinical manifestations. Epidemiology. Investigative techniques. Etiology Coronary Vessels - cytology Dopamine Agonists - pharmacology Fenoldopam - pharmacology Fundamental and applied biological sciences. Psychology Hemodynamics. Rheology Humans Hypertension - metabolism Hypertension - physiopathology Kidney Tubules, Proximal - drug effects Kidney Tubules, Proximal - metabolism Male Medical sciences Mesenteric Arteries - physiopathology Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - metabolism Precipitin Tests Rats Rats, Inbred SHR Rats, Inbred WKY Receptors, Dopamine D1 - agonists Receptors, Dopamine D1 - metabolism Receptors, Dopamine D2 - agonists Receptors, Dopamine D2 - metabolism Receptors, Dopamine D3 Vasodilation Vertebrates: cardiovascular system |
| title | Aberrant D1 and D3 Dopamine Receptor Transregulation in Hypertension |
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