{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:56Z","timestamp":1787013956814,"version":"build-2736575974"},"reference-count":59,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2017,5,10]],"date-time":"2017-05-10T00:00:00Z","timestamp":1494374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS PI070509"],"award-info":[{"award-number":["FIS PI070509"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2013\u201045362\u2010R"],"award-info":[{"award-number":["SAF2013\u201045362\u2010R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003508","name":"Universitat de Val\u00e8ncia","doi-asserted-by":"publisher","award":["UV\u2010INV\u2010AE11\u201042176"],"award-info":[{"award-number":["UV\u2010INV\u2010AE11\u201042176"]}],"id":[{"id":"10.13039\/501100003508","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      A NO\u2010mediated desensitization of vasoconstrictor responses evoked by stimulation of \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenoceptors has been reported in different vessels. We investigated the involvement of each \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenoceptor subtype and constitutive NOS isoforms and the influence of ageing and hypertension on this process.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Wistar and spontaneously hypertensive rats (SHR), 16, 32, 52 and 72\u00a0weeks\u2010old, were used to evaluate the desensitization process. Expression of \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenoceptor subtypes, endothelial NOS (eNOS) and neuronal NOS (nNOS) were determined in rat aorta and left ventricle (LV). Expression levels were also evaluated in LV of a group of heart failure patients with a wide age range.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Repeated application of phenylephrine decreased subsequent \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenoceptor\u2010mediated vasoconstriction by increasing nNOS protein expression in aorta, but not in tail or mesenteric resistance arteries, where mRNA levels of nNOS were undetectable. This desensitization process disappeared in the absence of endothelium or in the presence of L\u2010NAME (100\u00a0\u03bcM), nNOS inhibitors, SMTC (1\u00a0\u03bcM) and TRIM (100\u00a0\u03bcM), and 5\u2010methylurapidil (100\u00a0nM, \u03b1\n                      <jats:sub>1A<\/jats:sub>\n                      \u2010antagonist), but not BMY7378 (10\u00a0nM, \u03b1\n                      <jats:sub>1D<\/jats:sub>\n                      \u2010antagonist). The \u03b1\n                      <jats:sub>1A<\/jats:sub>\n                      \/nNOS\u2010mediated desensitization was absent in aged SHR and Wistar animals, where the expression of \u03b1\n                      <jats:sub>1A<\/jats:sub>\n                      \u2010adrenoceptors was reduced in aorta and LV. In human LV, a negative correlation was found between age and \u03b1\n                      <jats:sub>1A<\/jats:sub>\n                      \u2010adrenoceptor expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      The \u03b1\n                      <jats:sub>1A<\/jats:sub>\n                      \u2010adrenoceptor subtype, through endothelial nNOS\u2010derived NO, may act as a physiological \u2018brake\u2019 against the detrimental effects of excessive \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenoceptor\u2010mediated vasoconstriction. Reduced \u03b1\n                      <jats:sub>1A<\/jats:sub>\n                      \u2010adrenoceptor\u2010 and nNOS\u2010mediated desensitization in aged patients could be involved in the age\u2010dependent elevation of adrenergic activity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.13800","type":"journal-article","created":{"date-parts":[[2017,3,29]],"date-time":"2017-03-29T23:32:42Z","timestamp":1490830362000},"page":"2015-2030","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Activation of \u03b1\n                    <sub>1A<\/sub>\n                    \u2010adrenoceptors desensitizes the rat aorta response to phenylephrine through a neuronal NOS pathway, a mechanism lost with ageing"],"prefix":"10.1111","volume":"174","author":[{"given":"Cristina","family":"Arce","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Farmacia 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