benzofurans and Hypertension--Renal

Previous studies have demonstrated that a natural product of celery seeds, 3‑n‑butylphthalide (NBP), has significant antihypertensive effects that are widely utilized in Chinese traditional medicine. The present study aimed to investigate the effects of NBP on hypertensive nephropathy, as well as the mechanisms underlying this disease in spontaneously hypertensive rats (SHRs). SHRs were treated orally with saline, NBP (15 or 30 mg/kg) or losartan (10 mg/kg) daily for 20 weeks, during which time blood pressure was measured every four weeks. At the end of the 20‑week treatment, blood and urine samples were collected for biochemical analysis, and kidney tissues were obtained for histopathological analysis and immunohistochemistry. Enzyme‑linked immunosorbent assays and western blotting were used to analyze the expression of transforming growth factor (TGF)‑β1 in blood and kidney tissues, respectively. The results showed that NBP effectively attenuated progression of hypertensive nephropathy by decreasing urinary albumin excretion and blood urea nitrogen levels. It significantly decreased blood pressure (although less markedly than losartan) and the incidence of glomerulosclerosis. In addition, it alleviated tubular impairment and significantly decreased oxidative stress, as well as the expression of pro‑inflammatory cytokines and TGF-‑β1 in kidney tissues. In conclusion, the results suggested that NBP may slow the progression of hypertensive nephropathy by a variety of mechanisms.

Topics: Albumins; Animals; Antihypertensive Agents; Benzofurans; Blood Pressure; Blood Urea Nitrogen; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Hypertension, Renal; Immunohistochemistry; Interleukin-6; Kidney Glomerulus; Losartan; Male; NADPH Oxidases; Nephritis; Neuroprotective Agents; NF-kappa B; Rats; Rats, Inbred SHR; Transforming Growth Factor beta1

The purpose of the study is to establish a model of cold-induced stroke in hypertensive rats, and to study the preventive effect of dl-3n-butylphthalide ( NBP ) on stroke. Stroke-prone renovascular hypertension(RHRSP) was created in Sprague-Dawley rats. The animals were assigned randomly to NBP, aspirin treated and vehicle control group, with administration of the medications for 7 days, and then subjected to cold treatment in an environmentally controlled chamber for 3 days to induce the occurrence of stroke. The incidence of stroke, the volume of the brain lesion, patency of the microvessels by FITC-dextran perfusion and the number of microvessels by immunohisochemical detection of vwF were investigated. Cold induced different types of stroke in RHRSP. The incidence of ischemic stroke and the volume of the infarct were decreased, and the perfused microvessels were increased with NBP pretreatment. Our data suggest that NBP prevents cold-induced ischemic stroke via improvement of cerebral microvessels.

Topics: Animals; Aspirin; Benzofurans; Brain; Brain Ischemia; Cerebral Arteries; Cerebrovascular Circulation; Cold Temperature; Dextrans; Disease Models, Animal; Fluorescein-5-isothiocyanate; Hypertension, Renal; Male; Microcirculation; Molecular Structure; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Stroke; Treatment Outcome

The cardiovascular profile of the angiotensin AT1 receptor antagonist, GR138950, and the influence of potential compensatory homeostatic mechanisms on this profile, were investigated in renal artery ligated hypertensive (RALH) rats. GR138950 caused a marked reduction in blood pressure associated with immediate tachycardia in conscious RALH rats. The antihypertensive action of GR138950 appeared biphasic; an immediate fall in blood pressure, which plateaued within 1 h, and which was followed by a further slow decline that reached maximum between 5-7 h after administration. The tachycardia caused by GR138950 was attenuated by atenolol and was abolished by combined pretreatment with atenolol and atropine methyl nitrate. However, the antihypertensive profile of GR138950 was unchanged by these pretreatments. The resting blood pressure and the antihypertensive effect of GR138950, in RALH rats, were unaffected by the vasopressin V1 receptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylene propionyl(1)-O-Me-Tyr2,Arg8]-vasopressin. Thus, vasopressinergic mechanisms are not involved in either maintaining blood pressure in RALH rats, or in compensating for the fall in blood pressure caused by GR138950. In anaesthetized RALH rats, GR138950 caused a marked fall in blood pressure that was accompanied by an increase in heart rate along with sustained increases in renal and splanchnic sympathetic nerve activity. In summary, the biphasic fall in blood pressure evoked by GR138950 in RALH rats can not be explained on the basis of changes in autonomic control of the heart, alteration of vasopressin-mediated vasoconstrictor mechanisms or overall suppression of central sympathetic outflow. Rather, increased vasoconstrictor tone might serve to oppose the initial fall in blood pressure.

Topics: Angiotensin Receptor Antagonists; Animals; Anti-Arrhythmia Agents; Antidiuretic Hormone Receptor Antagonists; Antihypertensive Agents; Arginine Vasopressin; Atropine; Benzofurans; Blood Pressure; Heart Rate; Homeostasis; Hormone Antagonists; Hypertension, Renal; Kidney; Male; Rats; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Splanchnic Nerves; Sympathetic Nervous System

Topics: Adult; Benzbromarone; Benzofurans; Glomerulonephritis; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Nephrectomy; Polycystic Kidney Diseases; Proteinuria; Pyelonephritis; Renal Dialysis; Uric Acid