{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:19:19Z","timestamp":1792199959187,"version":"4.4.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T00:00:00Z","timestamp":1277942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The role of vascular sympatholytic activity of carvedilol in its antihypertensive effect in NG-nitro-l-arginine methyl ester (L-NAME) hypertensive rats was assessed by means of enantioselective pharmacokinetic\u2013pharmacodynamic (PK-PD) modelling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Wistar rats were randomly divided into two groups: control rats received tap water to drink for 2 weeks while L-NAME rats received L-NAME solution to drink for 2 weeks. The effects of carvedilol (1 and 5 mg\/kg i.v.) on blood pressure, heart rate and blood pressure variability were recorded. Enantioselective carvedilol plasma pharmacokinetics were studied by means of traditional blood sampling. The relationship between carvedilol concentrations and their hypotensive and bradycardic effects was established by means of PK-PD modelling. Vascular sympatholytic activity of carvedilol was assessed by the estimation of drug effects on low frequency blood pressure variability by means of spectral analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key findings<\/jats:title><jats:p>A dose-dependent increase in volume of distribution, as well as a greater volume of distribution and clearance of S-carvedilol as compared with the R-enantiomer was found in both experimental groups. Although the PK-PD properties of the S-carvedilol chronotropic effect were not altered in L-NAME rats, hypertensive rats showed greater potency and efficacy to the carvedilol hypotensive response. Greater potency of carvedilol for inhibition of sympathetic vascular activity was found in L-NAME rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Carvedilol showed enantioselective non-linear pharmacokinetic properties in both groups. An enhanced hypotensive activity of carvedilol was found in L-NAME hypertensive rats compared with control rats, which may be explained by the greater potency of carvedilol for sympathetic vascular tone inhibition.<\/jats:p><\/jats:sec>","DOI":"10.1211\/jpp.62.07.0010","type":"journal-article","created":{"date-parts":[[2015,9,3]],"date-time":"2015-09-03T20:54:24Z","timestamp":1441313664000},"page":"890-900","source":"Crossref","is-referenced-by-count":10,"title":["Enantioselective pharmacokinetic\u2013pharmacodynamic modelling of carvedilol in a<i>N<\/i>G-nitro-<scp>l<\/scp>-arginine methyl ester rat model of secondary hypertension"],"prefix":"10.1093","volume":"62","author":[{"given":"Carla Andrea","family":"Di Verniero","sequence":"first","affiliation":[{"name":"Department of Pharmacology , Buenos Aires,","place":["Argentina"]},{"name":"Institute of Physiopathology and Clinical Biochemistry , Buenos 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