A 62-year-old woman with activity-dependent two-to-one atrioventricular block (2:1AVB) and a normal left ventricular ejection fraction was referred to our department for the evaluation of exclusively exercise-induced marked symptoms. The treadmill test helped establish a clear correlation between 2:1AVB and symptoms. The test results demonstrated that exercise-induced marked symptoms were attributed to abrupt transient hypotension combined with relative bradycardia, probably due to increased diastolic mitral and tricuspid regurgitation because of 2:1AVB during moderate-to-heavy exercise. After pacemaker implantation for 2:1AVB, the symptoms and transient hypotension disappeared, and her exercise capacity improved.
Objective The activation of protein tyrosine kinases (PTKs) has been postulated to be involved in cell differentiation and proliferation. To elucidate the involvement of tyrosine kinase genes in normal and pathological conditions, we analysed the expression patterns of receptor-type PTKs in the normal and hypertensive hypertrophied heart in rats. Materials and methods Hypertrophied and normal rat hearts were obtained from hypertensive rats; deoxycorticosterone acetate (DOCA)-salt and 2 kidney-1 clip (2K-1C), and their sham-operated rats, respectively. A reverse transcription-polymerase chain reaction (RT-PCR) was performed using degenerated primers which were designed from highly conserved regions in the catalytic domains of receptor-type PTKs. The PCR products were ligated into a sequence vector, and subcloned by transforming bacteria. To compare the expression level of these PTK mRNAs in the normal and hypertrophied heart, we performed semi-competetive RT-PCR and immunohistochemical and Western blot analyses. Results Nucleotide sequencing of approximately 80 clones of PTKs revealed 10 receptor-type, five nonreceptor-type and two unknown types in the rat heart. Tie-2/Tek, Ryk, insulin-like growth factor-I receptor were abundantly expressed in the rat heart as members of receptor-type PTKs. Immunohistochemistry and RT-PCR demonstrated the presence of platelet-derived growth factor (PDGF)-α receptor, PDGF-β receptor and fibroblast growth factor-3 receptor in both normal and hypertrophied hearts. We also confirmed the presence of Flt-1, KDR/Flk-1, and their ligand vascular endothelial growth factor, c-Met and its ligand hepatocyte growth factor (HGF), and Tie-1, Tie-2/Tek by immunohistochemistry and RT-PCR. The co-expression of cardiac HGF and c-Met in hypertrophied hearts, especially in 2K-1C rats, was induced more intensively than that in DOCA-salt rats. Conclusion These findings suggest that HGF/c-Met interactions may play an important role in cardiac hypertrophy and remodeling, probably as a result of the activation of the local renin-angiotensin system.
Morning blood pressure (BP) level plays an important role in the incidence of cardiovascular disease. Recently, Kario, et al proposed the usefulness of ME difference (morning minus evening systolic BP) and ME average (average of morning and evening systolic BP) for the evaluation of antihypertensive treatment. Cilnidipine is a novel calcium channel blocker (CCB) that exerts inhibitory actions not only on L-type but also on N-type calcium channels. We investigated the effect of bedtime administration of cilnidipine (10 mg) in addition to the antihypertensive treatment for uncontrolled morning hypertension. Twenty-three hypertensive outpatients (13 males and 10 females; mean age, 66.9 years) with stable antihypertensive medication and uncontrolled morning BP were studied using self-measured BP monitoring in the morning and evening. Morning SBP (P < 0.001) and DBP (P < 0.001) decreased significantly from 150.2 ± 8.7 and 87.8 ± 9.3 to 132.7 ± 7.4 and 77.5 ± 8.5 mmHg, respectively, after the addition of cilnidipine. Morning heart rate did not change (63.3 ± 7.0 to 64.1 ± 9.4). The evening SBP, but not DBP, decreased significantly after treatment. Both the ME average (P < 0.001) and ME difference (P < 0.01) significantly decreased from 143.0 ± 9.2 and 14.3 ± 12.4 to 131.3 ± 7.2 and 2.8 ± 9.2 mmHg after treatment, respectively. The microalbuminuria decreased from 39.6 ± 13.2 to 27.3 ± 8.4 mg/g Cr. In conclusion, L-/N-type CCB cilnidipine may be useful for patients with uncontrollable morning hypertension by reducing both ME average and ME difference.
Title Genetic Analysis of Cardiacβ Myosin Heavy Chain(MHC)Gene in Seven Families with Hypertrophic Cardiomyopathy in Japan Author(s) Hayashi, Ikuo; Ashizawa, Naoto; Oku, Yasuhiko; Ozeki, Shinichiro; Ohtsuru, Akira; Yano, Katsusuke Citation Acta medica Nagasakiensia. 1994, 39(1-3), p.168-171 Issue Date 1994-10-25 URL http://hdl.handle.net/10069/15995 Right NAOSITE: Nagasaki University's Academic Output SITE
Angiotensin II (A II ) is a critical factor in cardiac remodeling which involves hypertrophy, fibroblast proliferation, and extracellular matrix production. However, little is known about the mechanism by which A II accelerates these re- sponses. Osteopontin is an acidic phosphoprotein with RGD (arginine-glycine-aspartate) sequences that are involved in the vascular smooth muscle cell remodeling process. We identified the presence of osteopontin mRNA and protein in cultured rat cardiac fibroblasts and its prominent regulation by A II (10 2 11 M). Osteopontin message levels were increased fourfold ( P , 0.01) and protein fivefold ( P , 0.05) at 24 h after addition of A II (10 2 7 M). This response was inhibited by the AT 1 receptor blocker, losartan. Osteopontin mRNA levels were increased in hypertrophied ventricles from ani- mals with renovascular hypertension (1.6-fold, P , 0.05) and aortic banding (2.9-fold, P , 0.05). To examine the function of osteopontin, we determined its effects on ( a ) the ability of cardiac fibroblasts to contract three-dimensional collagen gels and ( b ) cardiac fibroblast growth. A monoclonal antibody against osteopontin partially blocked A II -induced three-dimensional collagen gel contraction by cardiac fibro- blasts (64 6 4 vs. 86 6 5% in the presence of antibody, P , 0.05), while osteopontin itself promoted contraction of the gels by fibroblasts (71 6 5%, P , 0.05 compared with control). Ei- ther a monoclonal antibody against b 3 integrin which is a ligand for osteopontin or the RGD peptide blocked both A II and osteopontin-induced collagen gel contraction. Thus, the osteopontin RGD sequence binds to b 3 integrins on the fi- broblast to promote fibroblast binding to collagen. A II in- duced a threefold increase in DNA synthesis of cardiac fi- broblasts, which was completely blocked by antibodies against osteopontin and b 3 integrin, or by RGD peptide, but not by controls. Thus, A II -induced growth of cardiac fibro- blasts also requires osteopontin engagement of the b 3 inte- grin. Taken together, these results provide the first evidence that osteopontin is a potentially important mediator of A II regulation of cardiac fibroblast behavior in the cardiac re- modeling process. ( J. Clin. Invest. 1996. 98:2218-2227.) Key words: osteopontincardiac hypertrophyangiotensin II • cardiac fibroblastscollagen gel contraction
