Effects of dopamine and nitric oxide on arterial pressure and renal function in volume expansion

1. The aim of the present study was to investigate the role of dopamine (DA) in the hypotensive and renal effects of L-arginine during extracellular fluid volume expansion (10% bodyweight). 2. Animals were randomized to non-expanded and expanded groups. Both groups received different treatments: L-arginine (250 mg/kg, i.v.), N(G)-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg, i.v.), haloperidol (3 mg/kg, i.p.) and L-arginine + haloperidol (n = 8). Mean arterial pressure (MAP), diuresis, natriuresis, kaliuresis, glomerular filtration rate, renal plasma flow (RPF) and nitrite and nitrate (NO(x)) excretion were determined. 3. The increase in MAP induced by L-NAME was greater in expanded than in non-expanded rats (42 +/- 3 vs 32 +/- 3 mmHg, respectively; P < 0.01). Administration of haloperidol did not modify the L-arginine hypotensive effect. 4. Blockade of nitric oxide synthase diminished urine flow in non-expanded (4.15 +/- 0.56 vs 0.55 +/- 0.11 microL/min per 100 g; P < 0.01) and expanded animals (24.42 +/- 3.67 vs 17.85 +/- 2.16 microL/min per 100 g; P < 0.01). Diuresis induced by L-arginine was reduced by DA blockade in both non-expanded (17.15 +/- 2.11 vs 6.82 +/- 0.61 microL/min per 100 g; P < 0.01) and expanded animals (44.26 +/- 8.45 vs 25.43 +/- 5.12 microL/min per 100 g; P < 0.01). 5. Sodium excretion decreased with L-NAME treatment in non-expanded (0.22 +/- 0.03 vs 0.06 +/- 0.01 microEq/min per 100 g; P < 0.01) and expanded animals (3.72 +/- 0.70 vs 1.89 +/- 0.23 microEq/min per 100 g; P < 0.01). Natriuresis induced by L-arginine was diminished by haloperidol both in non-expanded (0.94 +/- 0.13 vs 0.43 +/- 0.04 microEq/min per 100 g; P < 0.01) and expanded rats (12.77 +/- 0.05 vs 3.53 +/- 0.75 microEq/min per 100 g; P < 0.01). Changes in kaliuresis changes seen following treatment with L-arginine, L-NAME and L-arginine + haloperidol followed a pattern similar to that observed for sodium excretion in both groups of rats. 6. L-arginine enhanced RPF in non-expanded animals (11.96 +/- 0.81 vs 14.52 +/- 1.05 mL/min per 100 g; P < 0.01). Glomerular filtration rate was increased by extracellular volume expansion (3.08 +/- 0.28 vs 5.42 +/- 0.46 mL/min per 100 g; P < 0.01). 7. The increase in NOx induced by acute volume expansion (0.18 +/- 0.03 vs 0.52 +/- 0.08 nmol/min per 100 g; P < 0.01) was diminished following the administration of haloperidol (0.52 +/- 0.08 vs 0.26 +/- 0.06 nmol/min per 100 g; P < 0.01). 8. Although DA does not participate in the actions of nitric oxide on vascular tone, both systems would play an important role in renal function adaptation during extracellular fluid volume expansion.     

Effect Of Age On Renal Functional And Orthostatic Vascular Response In Healthy Men

1. Few studies have been reported concerning the effect of ageing on renal functional and vascular responses to various stresses during ordinary life. In the present study, we examined the effect of age on changes in renal sodium handling and renal vascular resistance (RVR) in response to standing from a supine position in subjects with normal renal function. 2. We selected 43 healthy males in the second through to the seventh decade of life and gave them a constant dietary sodium intake before the study period. Renal function was estimated by standard clearance methods with the subject in a state of euvolaemia. 3. The mean daily urinary excretion of sodium was 236 ± 22 mEq. Standing from a supine position was associated with significant decreases (P < 0.0001) in creatinine clearance (from 125 ± 18 to 117 ± 19 mL/min per 1.73 m ² ), sodium excretion (from 178 ± 29 to 97 ± 23 μ Eq/min) and fractional excretion of sodium (from 1.02 ± 0.19 to 0.60 ± 0.13%). A significant increase (P < 0.0001) in the RVR index (from 0.11 ± 0.03 to 0.14 ± 0.04 units) was noted. Univariate analysis indicated that while the change in RVR associated with standing was significantly diminished (P < 0.05) in older subjects, orthostatic changes in other parameters associated with standing were minimally influenced by age. 4. In conclusion, although the renal vascular response is impaired in advanced age, the renal functional response to orthostasis is otherwise maintained in healthy elderly subjects under conditions of normal sodium intake and clinical euvolaemia.     

A Hypothesis About A Mechanism For The Programming Of Blood Pressure And Vascular Disease In Early Life

1. There is now a great deal of evidence that people whose weight at birth was low tend to have higher blood pressure and increased risk of death from cardiovascular disease as adults. 2. We argue that, in fetuses whose growth is impaired, synthesis of elastin in the walls of the aorta and large arteries is deficient and that this deficiency leads to permanent changes in the mechanical properties of these vessels. 3. Over a lifetime, such changes could predispose an individual to higher blood pressure and cardiovascular disease.     

Effects of chronic inhibition of nitric oxide synthase in the genetically hypertensive rat

1. The effects of graded inhibition of nitric oxide synthase (NOS) on blood pressure in the genetically hypertensive (GH) rat strain and NOS activity in regions of the brain (cerebellum, striatum, hippocampus, frontal cortex and medulla oblongata) as a measure of body NOS inhibition were studied. 2. Male GH and normotensive (N) rats (n = 7-10 per group) were given N(G)-nitro-L-arginine methyl ester (L-NAME; 2, 5, 10 or 20 mg/kg per day in drinking water) from age 7 weeks. Age- and weight-matched controls received water only. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method from age 6 weeks. By age 10 weeks, rats were killed and NOS activity was measured. 3. Some GH rats that received over 5 mg/kg per day L-NAME developed stroke-like symptoms and were killed before the end of the treatment period. 4. No difference in NOS activity was found between untreated N and GH strains but, in those that received treatment, a graded inhibition was observed with increasing L-NAME dose levels. The frontal cortex in the GH strain given 20 mg/kg per day L-NAME had NOS inhibition of 90% where the N strain had 73% inhibition. Similar results were seen in the other areas of the brain. 5. Left ventricular mass, weight related, was significantly greater in the GH compared with N and was further elevated by treatment with L-NAME. 6. The SBP at 10 weeks was significantly elevated in GH rats by NOS inhibition with L-NAME in a dose-dependent manner; 25% for 2 mg/kg per day, 31% for 20 mg/kg per day (P < 0.001). There was a non-significant increase in BP in the N-treated groups (average change of 7.5%). 7. Nitric oxide synthase inhibition causing increased SBP in GH rats suggests an abnormality in the nitric oxide-L-arginine pathway in this strain.     

联合治疗对早期糖尿病肾病血液流变学和肾功能的影响

目的:探讨阿魏酸哌嗪和黄芪注射液联合治疗对早期糖尿病肾病血液流变学和肾功能的影响.方法:将52例早期糖尿病肾病随机分为观察组和对照组,每组各26例.2组均采用饮食控制和糖尿病常规治疗,观察组加用阿魏酸哌嗪和黄芪注射液,疗程4周.结果:观察组血液流变学各项指标较治疗前显著下降(P<0.05),尿蛋白排泄率(UAER)、尿素氮(BUN)和血脂明显下降(P<0.05),且明显优于对照组(P<0.01).结论:阿魏酸哌嗪和黄芪注射液能改善早期糖尿病肾病血液流变学、血脂和微循环,减少尿蛋白的排除,减轻肾损害,改善肾功能.     

Renal Effects Of Efonidipine Hydrochloride, A New Calcium Antagonist, In Spontaneously Hypertensive Rats With Glomerular Injury

1. To obtain some insight into the renoprotective mechanism of the new calcium antagonist efonidipine hydrochloride, we evaluated the acute effects of efonidipine on proteinuria, glomerular haemodynamics and the tubuloglomerular feedback (TGF) mechanism in anaesthetized 24-25-week-old spontaneously hypertensive rats (SHR) with glomerular injury. 2. Efonidipine infusion at 10 micrograms/kg per h following a bolus dose of 10 micrograms/kg, i.v., reduced systemic blood pressure (BP) and renal vascular resistance, whereas renal plasma flow (RPF), glomerular filtration rate (GFR), filtration fraction, urine volume and urinary sodium excretion were unaltered. Urinary protein excretion was clearly diminished from 163 +/- 25 to 105 +/- 24 ng/min per g kidney weight. 3. Micropuncture experiments revealed that the maximal reduction of proximal stop-flow pressure (SFP), an index of glomerular capillary pressure (Pgc), induced by loop of Henle perfusion was significantly less with efonidipine treatment (6.7 +/- 1.0% of SFP with no loop flow) than in control (23.8 +/- 3.1%). In the presence of efonidipine, SFP at half-maximal reduction (SFP1/2max), which approximates Pgc at the in vivo steady state tubular flow rate, remained unchanged compared with control (36.9 +/- 0.8 vs 35.3 +/- 0.7 mmHg, respectively) and the slope of dependency on mean BP was not different between control and efonidipine. 4. These results indicate that efonidipine attenuates the TGF response in SHR by dilating the afferent arteriole, thus maintaining the level of RPF and GFR despite reduced renal perfusion pressure. Constant GFR and SFP1/2max under efonidipine suggest that single nephron GFR and Pgc remain unaltered and that a marked reduction in proteinuria is achieved without changes in single nephron GFR or Pgc of superficial nephrons.     

Effects Of Diabetes On Non-Adrenergic, Non-Cholinergic Relaxation Induced By Gaba And Electrical Stimulation In The Rat Isolated Duodenum

1. The effects of streptozotocin (STZ)-induced experimental diabetes on nitrergic-mediated responses to GABA and electrical field stimulation (EFS) have been evaluated in rat isolated duodenum. 2. In the presence of noradrenergic and cholinergic blockade, EFS (60 V, 1 ms, 0.1-32 Hz) induced frequency dependent relaxations of the preparation. GABA also caused submaximal relaxation of the rat duodenum. The relaxations induced by GABA and EFS were reduced in duodenal tissues from diabetic rats compared with control rats. 3. Neither ATP- nor sodium nitroprusside-induced relaxations were altered in diabetic duodenal tissues. GABA- and EFS-induced relaxations were inhibited by NG-nitro-L-arginine methyl ester (L-NAME; 300 mmol/L) in both diabetic and control rats. Although the inhibition caused by L-NAME of GABA- and EFS-induced relaxation was partially reversed by L-arginine (1 mmol/L), L-arginine alone had no effect on GABA- and EFS-induced relaxation in diabetic rats. 4. These results suggest that STZ-induced diabetes impairs non-adrenergic, non-cholinergic relaxation induced by EFS and GABA. Impairment of nitrergic innervation of the rat duodenum may contribute to the abnormalities of intestinal motility abnormalities associated with diabetes.     

血管加压素院前维持血压对非控制性出血性休克大鼠器官血流灌注及功能的影响

目的 观察早期应用精氨酸血管加压素(AVP)维持血压对非控制出血性休克大鼠器官血流灌注和功能的影响。方法 96只SD大鼠分为2组：AVP(5×10_-4 U/ml)组和低压复苏对照组。复制非控制出血性休克模型,观察早期(模拟院前救治阶段)应用AVP维持血压(50 mmHg,3 h)对休克动物的心功能指标和组织氧供/氧耗、肝/肾血流量、肝/肾功能及其线粒体功能的影响。结果 在院前救治阶段,应用AVP维持血压可明显改善心功能指标,提高心输出量和增加组织氧供/氧耗;同时AVP治疗也明显提高了肝血流量、改善肝线粒体功能,并明显降低了休克后升高的肝功能指标AST和ALT,其效果明显优于单纯低压复苏组。但AVP组的肾血流量低于低压复苏组,且两组间肾线粒体功能和肾功能指标(BUN和Scr)无明显差异。结论 院前救治阶段应用AVP可更有效的改善心功能、改善重要器官的血流灌注和线粒体功能,发挥抗休克作用。但AVP对肾功能的影响需进一步研究。