CHANGES IN THE IN VITRO PHARMACODYNAMIC PROPERTIES OF METOPROLOL IN ATRIA ISOLATED FROM SPONTANEOUSLY HYPERTENSIVE RATS (English)

Clinical and Experimental Pharmacology and Physiology

The present study addressed possible changes in the dissociation constant of metoprolol and its inverse agonist activity in spontaneously hypertensive rats (SHR). In addition, a possible correlation between cardiac hypertrophy and the inverse agonist activity of metoprolol was explored.

In order to determine the dissociation constant (expressed as the pKb) of metoprolol, a cumulative concentration–response curve to noradrenaline was constructed in the absence or presence of metoprolol (0.1, 1 or 10 µmol/L). In a second experiment, a cumulative concentration–response curve to metoprolol was constructed to determine its inverse agonist activity.

The ventricular weight of SHR was significantly greater compared with Wistar‐Kyoto (WKY) rats. A rightward shift of the concentration–response curve to noradrenaline was observed in SHR compared with WKY rats. The pKb of metoprolol was smaller in SHR compared with WKY rats (6.35 ± 0.14 vs 6.99 ± 0.12, respectively; P <� 0.05). No difference was observed in the maximal response (Emax) of the concentration–time effect of metoprolol in WKY rats and SHR (−29.1 ± 7.1 vs−28.2 ± 8.5%, respectively; n = 6 for both). However, the concentration of metoprolol eliciting a half‐maximal effect (expressed as the pEC50) was significantly smaller in SHR compared with WKY rats (4.82 ± 0.07 vs 5.29 ± 0.13, respectively; n = 6; P <� 0.05). Although a significant correlation (r = –0.876) between the ventricular weight/bodyweight (VW/BW) ratio and the pEC50 of the chronotropic effect of metoprolol was found, no relationship (r = –0.257) was found between the VW/BW ratio and Emax.

In summary, the present study provides the first evidence of a change in the in vitro pharmacodynamic properties of metoprolol in SHR. The sympathetic overactivity present in SHR not only reduces the positive chronotropic effect of noradrenaline, but also diminishes the constant dissociation of metoprolol from atrial β1‐adrenoceptors and its inverse agonist activity. A significant correlation between the VW/BW ratio and the inverse agonist potency of metoprolol was found, suggesting a possible link between cardiac hypertrophy and the reduction of the inverse agonist activity of metoprolol.

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Table of contents – Volume 34, Issue 3

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Tables of content are generated automatically and are based on records of articles contained that are available in the TIB-Portal index. Due to missing records of articles, the volume display may be incomplete, even though the whole journal is available at TIB.

135
CHOLESTEROL, STATINS AND CANCER
Brown, Andrew J | 2007
142
EFFICACY OF SARGASSUM POLYCYSTUM (PHAEOPHYCEAE) SULPHATED POLYSACCHARIDE AGAINST PARACETAMOL‐INDUCED DNA FRAGMENTATION AND MODULATION OF MEMBRANE‐BOUND PHOSPHATASES DURING TOXIC HEPATITIS
Raghavendran, HB / Sathivel, A / Yogeeta, RSSK / Devaki, T | 2007
148
FUNCTIONAL IMPAIRMENT OF CARDIAC TRANSIENT OUTWARD K+ CURRENT AS A RESULT OF ABNORMALLY ALTERED CELLULAR ENVIRONMENT
Du, Zhimin / Chaoqian, Xu / Shan, Hongli / Lu, Yanjie / Ren, Nanqi | 2007
153
ANGIOTENSIN II‐INDUCED GROWTH OF VASCULAR SMOOTH MUSCLE CELLS IS ASSOCIATED WITH MODULATION OF CELL SURFACE AREA AND PLATELET‐DERIVED GROWTH FACTOR RECEPTOR EXPRESSION
Kuma, Sosei / Oki, Eiji / Onohara, Toshihiro / Komori, Kimihiro / Maehara, Yoshihiko | 2007
161
CHANGES IN THE IN VITRO PHARMACODYNAMIC PROPERTIES OF METOPROLOL IN ATRIA ISOLATED FROM SPONTANEOUSLY HYPERTENSIVE RATS
Di Verniero, Carla / Höcht, Christian / Opezzo, Javier A W / Taira, Carlos A | 2007
166
CARDIOPROTECTIVE EFFECTS OF A NON‐ALCOHOLIC EXTRACT OF RED WINE DURING ISCHAEMIA AND REPERFUSION IN SPONTANEOUSLY HYPERTENSIVE RATS
Fantinelli, Juliana C / Mosca, Susana M | 2007
170
EFFECTS OF SHRIMP (MACROBRACIUM ROSENBERGII)‐DERIVED CHITOSAN ON PLASMA LIPID PROFILE AND LIVER LIPID PEROXIDE LEVELS IN NORMO‐ AND HYPERCHOLESTEROLAEMIC RATS
Hossain, Shahdat / Rahman, Azizur / Kabir, Yearul / Shams, Ali Ahmed / Afros, Fahmida / Hashimoto, Michio | 2007
177
NEUROPROTECTIVE EFFECTS OF DAURICINE AGAINST APOPTOSIS INDUCED BY TRANSIENT FOCAL CEREBRAL ISCHAEMIA IN RATS VIA A MITOCHONDRIAL PATHWAY
Li, Yan‐Hong / Gong, Pei‐Li | 2007
185
FIBRIN D‐DIMER FRAGMENTS ENHANCE INFLAMMATORY RESPONSES IN MACROPHAGES: ROLE IN ADVANCING ATHEROSCLEROSIS
Zhou, Dong / Yang, Peng‐Yuan / Zhou, Bin / Rui, Yao‐Cheng | 2007
191
DIFFERENTIAL DEVELOPMENT OF CARBACHOL‐INDUCED DESENSITIZATION IN RECEPTOR‐MEDIATED Ca2+ INFLUX AND Ca2+ RELEASE PATHWAYS IN SMOOTH MUSCLE OF GUINEA‐PIG TAENIA CAECI
Hishinuma, Shigeru / Matsumoto, Yukio / Sato, Ryo / Saito, Masaki | 2007
198
AMINO ACID AND FATTY ACID COMPOSITION OF AN AQUEOUS EXTRACT OF CHANNA STRIATUS (HARUAN) THAT EXHIBITS ANTINOCICEPTIVE ACTIVITY
Zakaria, ZA / Mat Jais, AM / Goh, YM / Sulaiman, MR / Somchit, MN | 2007
205
ANGIOTENSIN II INCREASES TISSUE‐SPECIFIC INHIBITOR OF METALLOPROTEINASE‐2 EXPRESSION IN RAT AORTIC SMOOTH MUSCLE CELLS IN VIVO: EVIDENCE OF A PRESSURE‐INDEPENDENT EFFECT
Castoldi, G / Di Gioia, CRT / Travaglini, C / Busca, G / Redaelli, S / Bombardi, C / Stella, A | 2007
210
STOBADINE PROTECTS RAT KIDNEY AGAINST ISCHAEMIA/REPERFUSION INJURY
Guz, Galip / Demirogullari, Billur / Ulusu, Nuray N / Dogu, Cihangir / Demirtola, Arzu / Kavutcu, Mustafa / Omeroglu, Suna / Stefek, Milan / Karasu, Cimen | 2007
217
POTENTIAL FOR ENDOTHELIN‐1‐MEDIATED IMPAIRMENT OF CONTRACTILE ACTIVITY IN HYPERTENSION
Kolka, Cathryn M / Rattigan, Stephen / Richards, Stephen M / Clark, Michael G | 2007
223
ROLE OF DORSAL HIPPOCAMPAL CANNABINOID RECEPTORS AND NITRIC OXIDE IN ANXIETY LIKE BEHAVIOURS IN RATS USING THE ELEVATED PLUS‐MAZE TEST
Roohbakhsh, Ali / Moghaddam, Akbar Hajizadeh / Massoudi, Roohollah / Zarrindast, Mohammad‐Reza | 2007
230
DIFFERENTIAL GROWTH INHIBITION AND INDUCTION OF APOPTOSIS BY GOSSYPOL BETWEEN HCT116 AND HCT116/BAX−/– COLORECTAL CANCER CELLS
Zhang, Manchao / Liu, Hongpeng / Tian, Zhenkun / Huang, Jenny / Remo, Mylene / Li, Q Quentin | 2007
238
BENEFICIAL EFFECT OF XANTHOANGELOL, A CHALCONE COMPOUND FROM ANGELICA KEISKEI, ON LIPID METABOLISM IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Ogawa, Hiroshi / Okada, Yukiko / Kamisako, Toshinori / Baba, Kimiye | 2007
244
AMELIORATIVE EFFECT OF CHLOROPHYTUM BORIVILIANUM ROOT ON LIPID METABOLISM IN HYPERLIPAEMIC RATS
Visavadiya, NP / Narasimhacharya, AVRL | 2007
250
ACUTE CORONARY LIGATION IN THE DOG INDUCES TIME‐DEPENDENT TRANSITIONAL CHANGES IN MITOCHONDRIAL CRISTA IN THE NON‐ISCHAEMIC VENTRICULAR MYOCARDIUM
McLachlan, Craig Steven / Almsherqi, Zakaria A / Chua, Kerin Sze Yi / Liew, Yu Ying / Low, Chwee Wah / Deng, Yuru | 2007
254
LETTER TO THE EDITOR
Palomeque, Jesús CG / Ruiz, Hugo G | 2007

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