{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T17:52:59Z","timestamp":1715536379172},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":4242,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1997,7]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The \u03b1<jats:sub>2a\/d<\/jats:sub>\u2010adrenoceptor subtype in the rat kidney modulates solute excretion (osmolar clearance). Since the kidney plays a role in chronic regulation of blood pressure, altered renal function may be implicated in the development of hypertension. A second alteration \u2010 that of the \u03b1<jats:sub>2a\/d<\/jats:sub>\u2010adrenoceptor subtype gene \u2010 has also been correlated with hypertension in rats and man.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We hypothesized that as a consequence of the altered \u03b1<jats:sub>2a\/d<\/jats:sub>\u2010adrenoceptor subtype gene previously shown in spontaneously hypertensive (SH) rats, the increase in osmolar clearance following stimulation of the renal \u03b1<jats:sub>2a\/d<\/jats:sub>\u2010subtype would be attenuated in SH rats as compared to normotensive Wistar rats. In contrast, based on the theory that such functional unresponsiveness of the \u03b1<jats:sub>2a\/d<\/jats:sub>\u2010subtype would be genetically determined, we further hypothesized that in one kidney\u2010one clip (1K\u20101C) rats, the response to stimulation of the renal \u03b1<jats:sub>2a\/d<\/jats:sub>\u2010subtype would be intact as compared to the normotensive Wistar 1K\u2010sham rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Male rats were unilaterally nephrectomized under ether anaesthesia. In the 1K\u20101C rats, a silver clip (diameter 0.254\u2003mm) was also placed around the left renal artery. On the experimental day, rats were administered pentobarbitone (50.0\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, i.p.). The carotid artery and jugular vein were cannulated for blood pressure monitoring and saline infusion. The ureter was catheterized for urine collection. A 31 gauge needle was advanced into the renal artery for infusion of the \u03b1<jats:sub>2a\/d<\/jats:sub>\u2010selective agonist, guanfacine (vehicle, 1.0, 3.0 and 10.0\u2003nmol\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003min<jats:sup>\u22121<\/jats:sup> in Wistar and SH rats; vehicle and 10.0\u2003nmol\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003min<jats:sup>\u22121<\/jats:sup> in Wistar 1K\u2010sham and 1K\u20101C rats).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In Wistar rats, guanfacine dose\u2010dependently increased urine flow and sodium excretion. An increase in osmolar clearance but not free water clearance was also observed. However, in SH rats guanfacine failed to alter urine flow, sodium excretion, osmolar and free water clearance. In contrast, in both Wistar 1K\u2010sham and 1K\u20101C rats, guanfacine increased urine flow rate. Again, this response was due solely to an increase in osmolar clearance. At these doses, guanfacine did not alter blood pressure or creatinine clearance during the experiment.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In summary, the ability of the \u03b1<jats:sub>2a\/d<\/jats:sub>\u2010adrenoceptor subtype to mediate an increase in osmolar clearance was absent in a genetic model of hypertension, the SH rats. This effect was intact in an acquired model of hypertension (1K\u20101C rats). This suggested a defective modulation of solute excretion in SH rats which was probably due to alteration of the \u03b1<jats:sub>2a\/d<\/jats:sub>\u2010subtype gene and not secondary to the elevated blood pressure. The altered \u03b1<jats:sub>2a\/d<\/jats:sub>\u2010subtype gene and function may therefore play a causal role in the pathogenesis of hypertension.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0701198","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T17:11:32Z","timestamp":1156525892000},"page":"861-866","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Renal <i>\u03b1<\/i><sub>2a\/d<\/sub>\u2010adrenoceptor subtype function: Wistar as compared to spontaneously hypertensive rats"],"prefix":"10.1111","volume":"121","author":[{"given":"H D","family":"Intengan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D D","family":"Smyth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"1181","article-title":"Dose selective dissociation of water and solute excretion after renal \u03b12\u2010adrenoceptor stimulation","volume":"247","author":"Blandford D.E.","year":"1988","journal-title":"J. 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