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Ventricular PKC‐ϵ and humoral signaling in DOCA‐Salt rats treated with labedipinedilol‐A
Author(s) -
Yeh JwuLai,
Liang JyhChong,
Liou ShwuFen,
Lin YoungTso,
Sheu ShengHsiung,
Lai WenTer,
Shin ShyiJang,
Chen IngJun
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10214
Subject(s) - atenolol , nifedipine , labetalol , prazosin , endocrinology , medicine , amlodipine , protein kinase c , pharmacology , atrial natriuretic peptide , chemistry , antagonist , receptor , blood pressure , calcium , signal transduction , biochemistry
Effects of oral antihypertensive monotherapy with labedipinedilol‐A, labetalol, atenolol, amlodipine, prazosin (20 mg kg −1 day −1 ), and short‐acting nifedipine (3 mg kg −1 day −1 ) on DOCA‐salt‐induced translocation of ventricular protein kinase C‐ϵ(PKC‐ϵ), humoral signaling, and the cardiovascular system were investigated in rats for 4 weeks. The triple blocking activities of labedipinedilol‐A (α/β‐adrenoceptor blockade and calcium entry blockade) were compared with single blocking activities of selective drugs. Cytosolic PKC‐ϵ immunoreactivity was decreased by labedipinedilol‐A, short‐acting nifedipine, amlodipine, prazosin, labetalol, atenolol, and losartan. Membranous PKC‐ϵ immunoreactivity was significantly decreased by labedipinedilol‐A, amlodipine, prazosin, labetalol, and atenolol. Labedipinedilol‐A and prazosin more potently decreased membranous than cytosolic PKC‐ϵ expression. Labedipinedilol‐A, labetalol, and atenolol effectively inhibited DOCA‐salt‐induced increases in angiotensin II (Ang II). All antihypertensive agents reduced endothelin‐1 (ET‐1) levels in urine and cardiac weight growth. Treatments with labedipinedilol‐A, labetalol, atenolol, and amlodipine normalized DOCA‐salt‐induced ANP increases. Prazosin did not decrease ANP. Short‐acting nifedipine elevated ANP. During long‐term antihypertensive therapy in DOCA‐salt hypertensive rats, single blockade drugs did not fully inhibit ventricular PKC‐ϵ translocation or Ang II, ET‐1, and ANP humoral signaling. However, triple blockade labedipinedilol‐A therapy had a wide range of α/β‐adrenergic receptor and calcium channel inhibitory activities, including diminished reflux tachycardia, inhibition of PKC‐ϵ translocation, and reduction of Ang II, ET‐1, and ANP formation. Drug Dev. Res. 59:307–315, 2003. 2003 Wiley‐Liss, Inc.