Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response
A biphasic cardiovascular response to bolus i.v. injection of human urotensin II (hUII, 3 nmol kg−1) in conscious, male, Sprague–Dawley (SD) rats was identified and underlying mechanisms were explored. Initially (0–5 min) there was tachycardia, hypotension and mesenteric and hindquarters vasodilatat...
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| Veröffentlicht in: | British journal of pharmacology 2004-10, Vol.143 (3), p.422-430 |
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| description | A biphasic cardiovascular response to bolus i.v. injection of human urotensin II (hUII, 3 nmol kg−1) in conscious, male, Sprague–Dawley (SD) rats was identified and underlying mechanisms were explored. Initially (0–5 min) there was tachycardia, hypotension and mesenteric and hindquarters vasodilatation; later (30–120 min), tachycardia, hindquarters vasodilatation and a modest rise in blood pressure occurred.
Pretreatment with indomethacin or NG nitro‐L‐arginine methylester (L‐NAME) reduced the mesenteric vasodilator response to hUII, and abolished the late tachycardia and hindquarters vasodilatation. Indomethacin also abolished the hypotension and early hindquarters vasodilatation, and substantially reduced the initial tachycardia. Indomethacin and L‐NAME together prevented all haemodynamic responses to hUII.
Inhibition of inducible NOS had no effect on responses to hUII, whereas inhibition of neuronal NOS reduced the delayed tachycardic response to hUII but did not significantly affect the vasodilatation. Only the initial tachycardic response to hUII was antagonised by propranolol.
In spontaneously hypertensive rats (SHR), the initial haemodynamic responses to hUII were qualitatively similar to those in SD rats, although there was also a modest renal vasodilatation. The secondary response comprised a smaller tachycardia and a small rise in blood pressure, with no significant hindquarters vasodilatation.
Haemodynamic responses to hUII were not enhanced by endothelin and angiotensin receptor antagonism in either SD rats or in SHRs.
One interpretation of these results is that the primary response to bolus injection of hUII is prostanoid‐ or prostanoid‐ and NO‐mediated (mesenteric vasodilatation) and that this triggers secondary events, which are dependent on eNOS (hindquarters vasodilatation) and neuronal NOS (tachycardia).
British Journal of Pharmacology (2004) 143, 422–430. doi:10.1038/sj.bjp.0705954 |
| doi_str_mv | 10.1038/sj.bjp.0705954 |
| format | Article |
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Pretreatment with indomethacin or NG nitro‐L‐arginine methylester (L‐NAME) reduced the mesenteric vasodilator response to hUII, and abolished the late tachycardia and hindquarters vasodilatation. Indomethacin also abolished the hypotension and early hindquarters vasodilatation, and substantially reduced the initial tachycardia. Indomethacin and L‐NAME together prevented all haemodynamic responses to hUII.
Inhibition of inducible NOS had no effect on responses to hUII, whereas inhibition of neuronal NOS reduced the delayed tachycardic response to hUII but did not significantly affect the vasodilatation. Only the initial tachycardic response to hUII was antagonised by propranolol.
In spontaneously hypertensive rats (SHR), the initial haemodynamic responses to hUII were qualitatively similar to those in SD rats, although there was also a modest renal vasodilatation. The secondary response comprised a smaller tachycardia and a small rise in blood pressure, with no significant hindquarters vasodilatation.
Haemodynamic responses to hUII were not enhanced by endothelin and angiotensin receptor antagonism in either SD rats or in SHRs.
One interpretation of these results is that the primary response to bolus injection of hUII is prostanoid‐ or prostanoid‐ and NO‐mediated (mesenteric vasodilatation) and that this triggers secondary events, which are dependent on eNOS (hindquarters vasodilatation) and neuronal NOS (tachycardia).
British Journal of Pharmacology (2004) 143, 422–430. doi:10.1038/sj.bjp.0705954</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0705954</identifier><identifier>PMID: 15339862</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Amidines - pharmacology ; Animals ; Arginine - analogs & derivatives ; Arginine - pharmacology ; Arginine Vasopressin - pharmacology ; Benzylamines - pharmacology ; Biological and medical sciences ; Blood Pressure - drug effects ; Cardiovascular Physiological Phenomena - drug effects ; Cardiovascular System - drug effects ; Cardiovascular System - physiopathology ; Consciousness ; cyclooxygenase ; Enzyme Inhibitors - pharmacology ; haemodynamics ; Heart Rate - drug effects ; Hemodynamics - drug effects ; Humans ; Indans - pharmacology ; Indomethacin - pharmacology ; Injections, Intravenous ; Losartan - pharmacology ; Male ; Medical sciences ; NG-Nitroarginine Methyl Ester - pharmacology ; nitric oxide ; Nitric Oxide Synthase - antagonists & inhibitors ; Pharmacology. Drug treatments ; Propranolol - pharmacology ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Rats, Inbred SHR ; Rats, Inbred WKY ; Rats, Sprague-Dawley ; spontaneously hypertensive rats ; Urotensin II ; Urotensins - administration & dosage ; Urotensins - pharmacology ; Vasoconstriction - drug effects ; Vasoconstrictor Agents - pharmacology ; Vasodilation - drug effects ; Vasodilator Agents - pharmacology</subject><ispartof>British journal of pharmacology, 2004-10, Vol.143 (3), p.422-430</ispartof><rights>2004 British Pharmacological Society</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Oct 2004</rights><rights>Copyright 2004, Nature Publishing Group 2004 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5822-6374ae5d2fcd3bb24639401d0bcef7f41809e43459db410c228da755f2abc89a3</citedby><cites>FETCH-LOGICAL-c5822-6374ae5d2fcd3bb24639401d0bcef7f41809e43459db410c228da755f2abc89a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1575352/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1575352/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16195900$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15339862$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gardiner, Sheila M</creatorcontrib><creatorcontrib>March, Julie E</creatorcontrib><creatorcontrib>Kemp, Philip A</creatorcontrib><creatorcontrib>Bennett, Terence</creatorcontrib><title>Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>A biphasic cardiovascular response to bolus i.v. injection of human urotensin II (hUII, 3 nmol kg−1) in conscious, male, Sprague–Dawley (SD) rats was identified and underlying mechanisms were explored. Initially (0–5 min) there was tachycardia, hypotension and mesenteric and hindquarters vasodilatation; later (30–120 min), tachycardia, hindquarters vasodilatation and a modest rise in blood pressure occurred.
Pretreatment with indomethacin or NG nitro‐L‐arginine methylester (L‐NAME) reduced the mesenteric vasodilator response to hUII, and abolished the late tachycardia and hindquarters vasodilatation. Indomethacin also abolished the hypotension and early hindquarters vasodilatation, and substantially reduced the initial tachycardia. Indomethacin and L‐NAME together prevented all haemodynamic responses to hUII.
Inhibition of inducible NOS had no effect on responses to hUII, whereas inhibition of neuronal NOS reduced the delayed tachycardic response to hUII but did not significantly affect the vasodilatation. Only the initial tachycardic response to hUII was antagonised by propranolol.
In spontaneously hypertensive rats (SHR), the initial haemodynamic responses to hUII were qualitatively similar to those in SD rats, although there was also a modest renal vasodilatation. The secondary response comprised a smaller tachycardia and a small rise in blood pressure, with no significant hindquarters vasodilatation.
Haemodynamic responses to hUII were not enhanced by endothelin and angiotensin receptor antagonism in either SD rats or in SHRs.
One interpretation of these results is that the primary response to bolus injection of hUII is prostanoid‐ or prostanoid‐ and NO‐mediated (mesenteric vasodilatation) and that this triggers secondary events, which are dependent on eNOS (hindquarters vasodilatation) and neuronal NOS (tachycardia).
British Journal of Pharmacology (2004) 143, 422–430. doi:10.1038/sj.bjp.0705954</description><subject>Amidines - pharmacology</subject><subject>Animals</subject><subject>Arginine - analogs & derivatives</subject><subject>Arginine - pharmacology</subject><subject>Arginine Vasopressin - pharmacology</subject><subject>Benzylamines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Cardiovascular Physiological Phenomena - drug effects</subject><subject>Cardiovascular System - drug effects</subject><subject>Cardiovascular System - physiopathology</subject><subject>Consciousness</subject><subject>cyclooxygenase</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>haemodynamics</subject><subject>Heart Rate - drug effects</subject><subject>Hemodynamics - drug effects</subject><subject>Humans</subject><subject>Indans - pharmacology</subject><subject>Indomethacin - pharmacology</subject><subject>Injections, Intravenous</subject><subject>Losartan - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>NG-Nitroarginine Methyl Ester - pharmacology</subject><subject>nitric oxide</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Pharmacology. Drug treatments</subject><subject>Propranolol - pharmacology</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Rats, Inbred Lew</subject><subject>Rats, Inbred SHR</subject><subject>Rats, Inbred WKY</subject><subject>Rats, Sprague-Dawley</subject><subject>spontaneously hypertensive rats</subject><subject>Urotensin II</subject><subject>Urotensins - administration & dosage</subject><subject>Urotensins - pharmacology</subject><subject>Vasoconstriction - drug effects</subject><subject>Vasoconstrictor Agents - pharmacology</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc1v1DAUxC0EokvhyhFFSHDL4s_YviDRCuhKleBAuVovjsM6JHawN0X73-NqIwpcOFn2-73xjAah5wRvCWbqTR627TBvscRCC_4AbQiXTS2YIg_RBmMsa0KUOkNPch4wLkMpHqMzIhjTqqEb9PUijkuufBicPfgYqthX-2WCUN3sduW5sjFk62NhEhxy5W7jd5crqFo_7yF7W-3BTbE7BpjKJbk8lwX3FD3qYczu2Xqeo5sP779cXtXXnz7uLt9d11YoSuuGSQ5OdLS3HWtbyhumOSYdbq3rZc-JwtpxxoXuWk6wpVR1IIXoKbRWaWDn6O1Jd17ayXXWhUOC0czJT5COJoI3f0-C35tv8dYQIQUTtAi8XgVS_LG4fDCTz9aNIwRXQpumKYYkuwNf_gMOcUmhhDOUSKIp17JA2xNkU8w5uf63E4LNXV8mD6b0Zda-ysKLP_3f42tBBXi1ApAtjH2CYH2-5xqihca4cOzE_fSjO_7nW3Px-aoEo-wXVyav9w</recordid><startdate>200410</startdate><enddate>200410</enddate><creator>Gardiner, Sheila M</creator><creator>March, Julie E</creator><creator>Kemp, Philip A</creator><creator>Bennett, Terence</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200410</creationdate><title>Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response</title><author>Gardiner, Sheila M ; March, Julie E ; Kemp, Philip A ; Bennett, Terence</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5822-6374ae5d2fcd3bb24639401d0bcef7f41809e43459db410c228da755f2abc89a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Amidines - pharmacology</topic><topic>Animals</topic><topic>Arginine - analogs & derivatives</topic><topic>Arginine - pharmacology</topic><topic>Arginine Vasopressin - pharmacology</topic><topic>Benzylamines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Cardiovascular Physiological Phenomena - drug effects</topic><topic>Cardiovascular System - drug effects</topic><topic>Cardiovascular System - physiopathology</topic><topic>Consciousness</topic><topic>cyclooxygenase</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>haemodynamics</topic><topic>Heart Rate - drug effects</topic><topic>Hemodynamics - drug effects</topic><topic>Humans</topic><topic>Indans - pharmacology</topic><topic>Indomethacin - pharmacology</topic><topic>Injections, Intravenous</topic><topic>Losartan - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>NG-Nitroarginine Methyl Ester - pharmacology</topic><topic>nitric oxide</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Pharmacology. Drug treatments</topic><topic>Propranolol - pharmacology</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Rats, Inbred Lew</topic><topic>Rats, Inbred SHR</topic><topic>Rats, Inbred WKY</topic><topic>Rats, Sprague-Dawley</topic><topic>spontaneously hypertensive rats</topic><topic>Urotensin II</topic><topic>Urotensins - administration & dosage</topic><topic>Urotensins - pharmacology</topic><topic>Vasoconstriction - drug effects</topic><topic>Vasoconstrictor Agents - pharmacology</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gardiner, Sheila M</creatorcontrib><creatorcontrib>March, Julie E</creatorcontrib><creatorcontrib>Kemp, Philip A</creatorcontrib><creatorcontrib>Bennett, Terence</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>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gardiner, Sheila M</au><au>March, Julie E</au><au>Kemp, Philip A</au><au>Bennett, Terence</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2004-10</date><risdate>2004</risdate><volume>143</volume><issue>3</issue><spage>422</spage><epage>430</epage><pages>422-430</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>A biphasic cardiovascular response to bolus i.v. injection of human urotensin II (hUII, 3 nmol kg−1) in conscious, male, Sprague–Dawley (SD) rats was identified and underlying mechanisms were explored. Initially (0–5 min) there was tachycardia, hypotension and mesenteric and hindquarters vasodilatation; later (30–120 min), tachycardia, hindquarters vasodilatation and a modest rise in blood pressure occurred.
Pretreatment with indomethacin or NG nitro‐L‐arginine methylester (L‐NAME) reduced the mesenteric vasodilator response to hUII, and abolished the late tachycardia and hindquarters vasodilatation. Indomethacin also abolished the hypotension and early hindquarters vasodilatation, and substantially reduced the initial tachycardia. Indomethacin and L‐NAME together prevented all haemodynamic responses to hUII.
Inhibition of inducible NOS had no effect on responses to hUII, whereas inhibition of neuronal NOS reduced the delayed tachycardic response to hUII but did not significantly affect the vasodilatation. Only the initial tachycardic response to hUII was antagonised by propranolol.
In spontaneously hypertensive rats (SHR), the initial haemodynamic responses to hUII were qualitatively similar to those in SD rats, although there was also a modest renal vasodilatation. The secondary response comprised a smaller tachycardia and a small rise in blood pressure, with no significant hindquarters vasodilatation.
Haemodynamic responses to hUII were not enhanced by endothelin and angiotensin receptor antagonism in either SD rats or in SHRs.
One interpretation of these results is that the primary response to bolus injection of hUII is prostanoid‐ or prostanoid‐ and NO‐mediated (mesenteric vasodilatation) and that this triggers secondary events, which are dependent on eNOS (hindquarters vasodilatation) and neuronal NOS (tachycardia).
British Journal of Pharmacology (2004) 143, 422–430. doi:10.1038/sj.bjp.0705954</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>15339862</pmid><doi>10.1038/sj.bjp.0705954</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amidines - pharmacology Animals Arginine - analogs & derivatives Arginine - pharmacology Arginine Vasopressin - pharmacology Benzylamines - pharmacology Biological and medical sciences Blood Pressure - drug effects Cardiovascular Physiological Phenomena - drug effects Cardiovascular System - drug effects Cardiovascular System - physiopathology Consciousness cyclooxygenase Enzyme Inhibitors - pharmacology haemodynamics Heart Rate - drug effects Hemodynamics - drug effects Humans Indans - pharmacology Indomethacin - pharmacology Injections, Intravenous Losartan - pharmacology Male Medical sciences NG-Nitroarginine Methyl Ester - pharmacology nitric oxide Nitric Oxide Synthase - antagonists & inhibitors Pharmacology. Drug treatments Propranolol - pharmacology Rats Rats, Inbred F344 Rats, Inbred Lew Rats, Inbred SHR Rats, Inbred WKY Rats, Sprague-Dawley spontaneously hypertensive rats Urotensin II Urotensins - administration & dosage Urotensins - pharmacology Vasoconstriction - drug effects Vasoconstrictor Agents - pharmacology Vasodilation - drug effects Vasodilator Agents - pharmacology |
| title | Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response |
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