The antihypertensive effect of TC-81 ((+-)-3-(benzylmethylamino)-2,2-dimethylpropyl-methyl-4-(2-f luoro-5- nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate hydrochloride), a new calcium antagonist, was investigated in normotensive and hypertensive rats. By oral administration, the antihypertensive activity of TC-81 (ED20% in spontaneous hypertensive rats (SHR), DOCA-salt hypertensive rats and renal hypertensive rats were 0.37, 0.32, and 0.38 mg/kg p.o., respectively) was 7-14 times more potent in conscious hypertensive rats in comparison with nicardipine. Duration of the antihypertensive effect of TC-81 was about 2 times longer than that of nicardipine, and the response was elicited more slowly than that of nicardipine at an equipotent dose. Similar results were observed by intravenous injection, but the potency of TC-81 was only 3 times higher than that of nicardipine in anesthetized rats. Tolerance of the antihypertensive effect of TC-81 in long-term daily dosing and the rebound phenomenon after discontinuance of the treatment were not observed in hypertensive rats. TC-81, at a concentration of 10(-10)-3 x 10(-9) mol/l, inhibited the KCl-induced contraction of isolated rat vascular preparations. Moreover, TC-81 inhibited the norepinephrine-induced contraction of isolated SHR aorta preparation, but in isolated normotensive rat aorta, TC-81 inhibited the norepinephrine-induced contraction very little. From these observations, TC-81 can be characterized as having a strong, long-lasting, and slow-onset antihypertensive activity, especially by oral administration. Therefore, this new calcium antagonist may be useful for long-term antihypertensive therapy.
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Pharmacol Res
January 2025
Centro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, 88056-000 Florianópolis, Santa Catarina, Brazil. Electronic address:
Obesity is a global epidemic often associated with serious medical complications such as diabetes, hypertension and metabolic dysfunction-associated steatohepatitis. Considering the multifactorial nature of these diseases, medicinal plants could be a valuable therapeutic strategy as their phytoconstituents interact with multiple and relevant biological targets. In this context, Ilex paraguariensis emerges as a potential alternative to treat obesity and associated metabolic diseases since several studies have demonstrated its anti-inflammatory, anti-obesity and anti-diabetic effects.
View Article and Find Full Text PDFPLoS One
January 2025
Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand.
Although long-term high dietary sodium consumption often aggravates hypertension and bone loss, sodium in the intestinal lumen has been known to promote absorption of nutrients and other ions, e.g., glucose and calcium.
View Article and Find Full Text PDFHypertens Res
January 2025
Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Proteinuria, especially albuminuria, serves as an independent risk factor for progression in cardiovascular and renal diseases. Clinical and experimental studies have demonstrated that renal nerves contribute to renal dysfunction in arterial hypertension (AH). This study hypothesizes that renal nerves mediate the mechanisms of protein endocytosis by proximal tubule epithelial cells (PTEC) and glomerular function; with dysregulation of the renal nerves contributing to proteinuria in Wistar rats with renovascular hypertension (2-kidney, 1-clip model, 2K-1C).
View Article and Find Full Text PDFNan Fang Yi Ke Da Xue Xue Bao
January 2025
College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Objectives: To explore the mechanism of Granules (QDG) for alleviating brain damage in spontaneously hypertensive rats (SHRs).
Methods: Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks.
Elife
January 2025
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Estrogen significantly impacts women's health, and postmenopausal hypertension is a common issue characterized by blood pressure fluctuations. Current control strategies for this condition are limited in efficacy, necessitating further research into the underlying mechanisms. Although metabolomics has been applied to study various diseases, its use in understanding postmenopausal hypertension is scarce.
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