Kyoto University · Medicine
Professor Toshio Nishikimi's research lab specializes in cardiovascular and hormonal regulation, focusing on natriuretic peptides (ANP, BNP), adrenomedullin, and urocortin in the context of heart failure, hypertension, and cardiac remodeling. The lab investigates the local and systemic roles of these peptides as autocrine, paracrine, and endocrine factors, with particular emphasis on their production, signaling pathways, and pathophysiological functions in the heart and vasculature. Using both animal models and clinical studies, the lab explores molecular mechanisms underlying cardiac hypertrophy, fibrosis, and vascular dysfunction, aiming to identify novel therapeutic targets for cardiovascular diseases.
Figures are computed from collected data and may differ slightly.
Atrial natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP) are circulating hormones of cardiac origin that play an important role in the regulation of intravascular blood volume and vascular tone. The plasma concentrations of ANP and BNP are elevated in heart failure, and they are considered to compensate for heart failure because of their diuretic, natriuretic, and vasodilating actions and inhibitory effects on renin and aldosterone secretion. Evidence is also accumulating fr
Previous studies have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in essential hypertension. However, whether left ventricular geometry affects plasma ANP and BNP levels remains unknown. To investigate the effect of left ventricular geometry on plasma ANP and BNP levels in essential hypertension, we measured plasma ANP and BNP levels in 90 patients with essential hypertension. All patients were hospitalized, and fasting blood sam
Adrenomedullin is a novel hypotensive peptide, newly discovered in pheochromocytoma. Because immunoreactive adrenomedullin is present in human plasma, adrenomedullin may play a role in regulating blood pressure. A recent report showed that human adrenomedullin mRNA is expressed not only in pheochromocytoma but also in the normal adrenal medulla, kidney, lung, and ventricle. However, whether or not these organs actually release adrenomedullin into the circulation remains unknown. To investigate t
In the present study we investigated the form of expression, action, second messenger, and the cellular location of urocortin, a member of the corticotropin-releasing factor (CRF) family, in the heart. Urocortin mRNA, as shown by quantitative RT-PCR analysis, is expressed in the cultured rat cardiac nonmyocytes (NMC) as well as myocytes (MC) in the heart, whereas CRF receptor type 2beta (CRF-R2beta), presumed urocortin receptor mRNA, is predominantly expressed in MC compared with NMC. Urocortin
Plasma adrenomedullin (AM) levels are reportedly increased in heart failure, but whether the cardiac production and secretion of AM is increased in heart failure remains unknown. To investigate the sites of production and secretion of AM in heart failure, we measured plasma AM levels and peptide and mRNA levels of AM in various tissues in rats with heart failure. We also examined whether the heart actually secretes AM into the circulation in patients with heart failure. We measured plasma and ti
These results suggest that the Rho-Rho-kinase pathway may be partly responsible for the pathogenesis of hypertensive glomerulosclerosis independently of blood pressure in DS, and that chronic inhibition of the Rho-Rho-kinase pathway may be a new strategy for treating hypertensive nephrosclerosis.
The present study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in hypertensive renal failure and the mechanism by which chronic adrenomedullin infusion exerts its effects. Dahl salt-sensitive rats and Dahl salt-resistant rats were fed a high salt diet starting at 6 weeks of age. Recombinant human adrenomedullin or vehicle was infused for 7 weeks in 11-week-old Dahl salt-sensitive rats. Dahl salt-resistant rat was used as a control. After 7 weeks, unt
Adrenomedullin (AM) is a potent vasodilatory peptide originally discovered in human pheochromocytoma tissue. AM and AM gene expression are widely distributed in the cardiovascular system, including the kidney. The co-localization of AM and its receptor components such as calcitonin receptor-like receptor (CRLR), receptor activity modifying protein (RAMP)2 and RAMP3 in the kidney, heart, and vasculature suggests an important role for the peptide as a regulator of renal, cardiac, and vascular func
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