Relaxation of renal arterioles by parathyroid hormone and parathyroid hormone-related protein

The effects of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) on renal arteriolar tone and proximal tubule adenylate cyclase were examined. In both afferent and efferent arterioles, PTH produced concentration-dependent relaxation of norepinephrine-induced tone with EC50 values of 8.7 and 9.9 nmol/l, respectively. PTHrP also produced relaxations that were indistinguishable from PTH. In proximal convoluted tubules PTH and PTHrP stimulated adenylate cyclase to the same extent and with similar potencies. The PTH antagonist, bPTH(7-34), totally blocked PTH-induced arteriolar relaxation but had no effect on proximal tubule adenylate cyclase. The results demonstrate that PTH and PTHrP are potent relaxants of glomerular arterioles and that PTH receptors present on the renal microvasculature may differ from those present on proximal tubules.     

Serum luteinizing hormone response to administration of gonadotropin-releasing hormone to atrazine-treated gilts

The aim of the study was to evaluate the response of porcine luteinizing hormone (pLH) in serum to a single iv administration of gonadotropin-releasing hormone (GnRH) in atrazine-treated pigs. Experiments were performed in 15 mature female pigs (10 atrazine-treated, 5 control). From the onset of estrous (day 0), the pigs were given 1 mg atrazine/kg body mass in feed for 20 d of the estrous cycle. On the last day, blood samples were collected at min 0 from control and atrazine-exposed, and 5 atrazine-exposed pigs were immediatey given 100 mg GnRH iv. Blood samples were collected from atrazine-exposed and the GnRH-injected atrazine-exposed groups at 20, 30, 40 and 90 min and serum pLH concentrations were determined by radioimmunoassay. The administration of atrazine led to significant (p< 0.001) suppression of serum pLH concentrations (0.57 +/- 0.05 ng/ml) compared to control animals (2.24 +/- 0.20 ng/ml). The single iv GnRH administration to the atrazine-exposed pigs provoked significant pLH release at 20 and 30 min after GnRH administration, indicating attenuation of GnRH release in the atrazine-exposed animals was responsible for the suppression of serum pLH.     

Hormone metabolism and response of adenylate cyclase to parathyroid hormone in kidney

1. Incubation of parathyroid hormone with plasma membranes from rat kidney cortex resulted in rapid loss of all hormal activity. 2. Chick kidney membranes showed no ability to inactivate parathyroid hormone even with prolonged incubation. 3. Biologically active, labelled parathyroid hormone was degraded to fragments by rat kidney membranes, but not by chick kidney. 4. Hormone-responsive adenylate cyclase activity in a mixture of rat and chick kidney membranes was additive. 5. Parathyroid hormone bound specifically to chick kidney palsma membranes. 6. It is concluded that hormone in activation during incubation has little relevance to the effectiveness of parathyroid hormone in stimulating adenylate cyclase activity in kidney, and furthermore that failure of chick kidney to metabolize the hormone is not the explanation for the greater sensitivity of this species to the hormone.     

Urinary cyclic AMP response to bovine parathyroid hormone during treatment with neuroleptics

The urinary cyclic AMP response to bovine parathyroid hormone and urinary concentrating ability (max Uosm) after des-amino-D -arginine vasopressin were studies in nine volunteers and seven patients receiving long-term neuroleptic treatment. Max Uosm was lower in the patient group (770 ± 70 mosmol/kg) compared with the controls (948 ± 152 mosmol/kg) but the trend to a lower cAMP response to bovine PTH was not statistically significant. These results suggest that, although adenylate cyclase inhibition may contribute, other mechanisms are also important in the genesis of reduced uring concentrating ability in patients treated with psychotropic drugs.     

猕猴皮下注射重组人甲状旁腺激素的药代动力学研究

研究猕猴皮下注射重组人甲状旁腺激素[rhPTH（1-34）]后的药代动力学及生物利用度。猕猴皮下注射rhPTH（1-34）10，20和40ug/kg，静脉注射rhPTH（1-34）20ug/kg以及连续皮下注射rhPTH（1-34）40ug／kg（每天一次，连续14天），应用放免方法（IRMA）检测血浆样本中药物浓度，然后采用非房室模型计算药代动力学参数。IRMA方法检测血浆中rhPTH（1-34）的线性范围为0．027—2．22ng／mL。日内和日间精密度都小于15％，并且平均回收率约为93．0％±8．6％～116．5％±14．0％。猕猴皮下注射rhPTH（1—34）10，20和40ug／kg后，平均达峰时间Tmax分别为0．67，0．5和0．83h，峰浓度Cmax分别为1．85±0．05，3．23±0．25和7．15±1．19ng/mL,曲线下面积AUC（0-∞）分别为3．4±0．6，10．7±1．3和12．6±1．5ng／h／mL,末端相消除半衰期T1/2分别为0．72±0．10，1．15±0．10和1.03±0．06h。猕猴皮下注射mPTH（1-34）20ug／kg的绝对生物利用度为46．96％。连续注射猕猴rhPTH（1-34）后无药物蓄积。IRMA方法具有高灵敏度及专属性，适用于猕猴皮下注射mPTH（1-34）后的药物药代动力学研究。在给予剂量范围内，猕猴体内的rhPTH（1-34）药物代谢符合线性动力学特征。     

慢性肾衰竭大鼠甲状旁腺激素与肌钙蛋白的相关性分析

目的:探讨慢性肾衰竭(CRF)大鼠甲状旁腺激素(PTH)和肌钙蛋白(cTnI)的相关关系,旨在为临床早期诊断和治疗提供理论依据。方法:雌雄各半Wistar大鼠30只,先随机分为3组:正常组(6只);假手术组(6只),手术组(18只)。然后实行假手术和手术。手术组大鼠喂养4周后,检测血清尿素氮(BUN)、血清肌酐(Scr),确定CRF模型成熟后将其进一步分为CRF组和CRF组+罗钙全组(CRFL组)。用ELISA法检测PTH和cTnI,生化分析仪检测肾功能。结果:手术组和假手术组在大鼠体重、BUN、Scr差异均有显著性;随着给药时间的延长,手术组大鼠PTH和cT-nI均呈下降趋势,且CRF组高于同时间点CRFL组;PTH和cTnI呈直线相关关系。结论:CRF早期即可发生继发性甲状旁腺功能亢进,从而引起心血管系统病变;cTnI是反映CRF大鼠心肌损害的早期指标;重视降低血清PTH在CRF心血管并发症治疗中的作用。     

Inhibition of renal brush border phosphate transport and stimulation of renal gluconeogenesis by cyclic amp and parathyroid hormone

The aims of the study were to determine whether 8-bromo-cyclic AMP (8BcAMP) in vivo mimics the inhibitory action of parathyroid hormone (PTH) on phosphate transport across the brush border membrane (BBM) of the renal proximal tubule, and to examine whether changes in BBM transport are accompanied by changes in the rate of renal gluconeogenesis. Thyroparathyroidectomized dogs were anesthetized and equilibrated, and control urine collections were obtained prior to removing the left kidney. Subsequent intravenous infusion of 8BcAMP at 50 mg/hr for 2 hr increased fractional excretion of phosphate from 4 +/- 1 (controls) to 29 +/- 4% (P less than 0.001) without changing glomerular filtration. In BBM vesicles isolated from the renal cortex, the initial Na+-dependent transport of phosphate was decreased from 747 +/- 135 (controls) to 564 +/- 126 pmoles per mg per 0.25 min after 8BcAMP (P less than 0.025), but Na+-independent phosphate uptake and Na+-dependent L-proline uptake were not changed significantly. Renal gluconeogenesis in the same animals was increased from 2.5 +/- 0.3 (controls) to 5.3 +/- 0.5 mumoles glucose per g tissue per hr after infusion of 8BcAMP (P less than 0.001). Infusion of PTH, like 8BcAMP, inhibited BBM phosphate transport and stimulated renal gluconeogenesis. We conclude that the inhibitory action of cyclic AMP and PTH on BBM phosphate transport is accompanied by stimulation of gluconeogenesis which suggests, indirectly, that changes in gluconeogenesis may be part of the intracellular mechanism for regulating BBM phosphate uptake in response to certain stimuli.     

Use of renal artery infusion in dogs for evaluation of diuretics

In this paper we report on a series of experiments evaluating a model of renal artery infusion (RAI) as a screening technique for comparison of new diuretics, and test some assumptions underlying its use. The femoral artery and vein of Beagle dogs were catheterized for the infusion of solutions, measurement of arterial blood pressure and the sampling of arterial blood. The left kidney was isolated through a flank incision, and a 27 ga. needle, connected to PE10 tubing, was inserted into the renal artery for administration of test diuretics. Both ureters were catheterized for collection of urine. Effects on renal function were assessed during control, drug infusion, and recovery periods. At low doses, the loop diuretics, furosemide (FUR) and MK447, increased urinary excretion within the first 15 min of infusion. The effect of muzolimine, another loop diuretic, was delayed until about 45 min after initiation of infusion. Renal function returned to baseline after cessation of drug infusion. At high doses, excretion was increased by all the loop diuretics within the first 15 min of infusion. The response to muzolimine and MK447 was prolonged well into the recovery period, while that to furosemide returned promptly to baseline. Two distal diuretics, hydrochlorothiazide and amiloride, caused a significant increase in urinary excretion at both low and high doses. The magnitude of the response was significantly less than for the loop diuretics. Low doses of the loop diuretics had very little effect on the contralateral kidney; however, at high doses the excretion rate of the contralateral kidney was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of parathyroid hormone and related polypeptides on the heart and coronary circulation of dogs

The effects of parathyroid hormone and related polypeptides on the heart were examined using the canine heart-lung preparation supported by a donor. Synthetic bovine parathyroid hormone (PTH) containing 34 amino acids [PTH-(1--34)] and natural bovine PTH containing 84 amino acids [PTH-(1--84)] showed slight positive chronotropic and inotropic action and prominent coronary vasodilator action. The effects of the two compounds were very similar. The cardiac stimulatory action was not blocked by pindolol. The coronary vasodilation occurred without increase in the myocardial oxygen consumption, suggesting that it is due to a direct action on the coronary vasculature. All effects occurred soon after intra-arterial injection, lasted only about 20 min, and were not accompanied by changes in plasma Ca and Pi levels. Fragments of PTH, PTH-(24--34) containing 11 amino acids. PTH-(24--28) containing 5 amino acids, and PTH-(25--27) containing 3 amino acids showed very weak transient coronary dilatory action without cardiac stimulatory effects.     

Impaired renal response to portal infusion of hypertonic saline in adriamycin-treated rats

1. The hepatorenal reflex plays an important role in water and salt homeostasis by matching renal excretion to gastrointestinal absorption. This homeostatic mechanism is impaired in nephrotic rats. The present study tested the hypothesis that, in nephrotic rats, the renal sodium excretion response to hypertonic saline infusion is impaired due to decreased sensitivity of the hepatoportal sodium-sensing mechanism. 2. The present study was performed in control and adriamycin (ADR)-induced nephrotic syndrome rats. After baseline data collection, urinary sodium (U(Na)V) and potassium (U(K)V) excretion responses were tested following continuous infusion of hypertonic NaCl solution (20 μL/min for 30 min) into either the femoral or mesenteric vein. A second series of experiments tested hepatic and renal nerve responses to continuous mesenteric vein infusion of hypertonic NaCl (10 μL/s for 30 s). 3. Compared with control rats, nephrotic rats displayed significantly lower baseline U(Na)V and U(K)V excretion. In control rats, mesenteric compared with femoral vein infusion of hypertonic NaCl produced a more rapid and greater increase in U(Na)V. In contrast, in nephrotic rats, femoral and mesenteric vein infusion caused similar increases in U(Na)V and the maximum increases in U(Na)V to either route of infusion were much lower in nephrotic than control rats. Furthermore, portal hypertonic saline infusion caused greater increases in hepatic nerve activity and greater decreases in renal nerve activity in control compared with nephrotic rats. 4. These data suggest that, in rats, adriamycin treatment decreases hepatoportal sodium-sensing sensitivity, leading to marked impairment of hepatorenal reflex responses, potentially contributing to salt and water retention.     

甲状旁腺激素在终末期肾脏病患者血液透析中的意义

目的：探讨甲状旁腺激素(PTH)在终末期肾脏病患者血液透析中的意义。方法将100例长期行维持性血液透析的患者分为≤60岁、>60岁组,测定100例患者血液透析前后的PTH、血尿素氮(BUN)、血肌酐(SCr)、收缩压(SBP)、血红蛋白(Hb)、血浆白蛋白(Alb)、血磷(P3+)、血钙(Ca2+)水平等,分析BUN、SCr、SBP、Hb、Alb、P3+、Ca2+等与PTH的相关性。结果透析后,患者的BUN、SCr、SBP、P3+、PTH水平显著低于透析前(P<0.01),而Hb、Alb、Ca2+水平显著高于透析前(P<0.01);透析后,>60岁组患者的PTH水平低于≤60岁组患者(P<0.05);透析前,PTH与BUN、SCr、SBP呈正相关(r=0.148、0.651、0.326),与Hb、Alb、KT/V呈负相关(r=-0.621、0.337、0.598)。结论 PTH能对血液透析充分性进行有效评估。     

Effect of infusion administration set on the delivery rate and plasma concentration of nitroglycerin in dogs

A randomized crossover study with eight dogs was carried out to determine whether the in vitro difference observed in the delivery of nitroglycerin using polyvinyl chloride (PVC) and polyethylene (PE) infusion sets would result in a measurable difference in steady-state plasma concentration. At the same apparent infusion rate of 40 micrograms/min, PVC infusion sets produced steady-state plasma nitroglycerin concentrations that were only 40% of those generated with PE sets (p less than 0.0001). Attainment of steady-state drug levels appeared more rapid with the PE administration sets, but in three out of eight animals, these infusion systems appeared to produce a "bolus" dosing effect. PE sets did not reduce the variability in plasma nitroglycerin concentration observed with PVC sets.     

甲状旁腺素和甲状旁腺素相关肽在皮肤病中的研究进展

甲状旁腺素（ PTH）和甲状旁腺素相关肽（ PTHrP）是一类多肽类激素,它们具有相似的基因结构、相同的膜受体,在人体钙、磷代谢过程中起着重要的调节作用。 PTH和PTHrP及其受体除表达于肿瘤组织外,在皮肤、毛囊等正常组织也有表达。它们对表皮增殖分化、毛发生长的生理作用等方面,有望成为银屑病等常见皮肤病的治疗新靶点。     

Autoregulation of renal blood flow during the infusion of acetylcholine or carbachol in anaesthetized dogs

Whether renal blood flow autoregulation is abolished by acetylcholine was re-examined by kidney perfusion experiments in anaesthetized dogs. Renal blood flow was dose-dependently increased by the renal arterial infusion of acetylcholine (2 and 5 micrograms min-1) or another muscarinic agent, carbachol (2 and 5 micrograms min-1) and was maintained at an increased level during the infusion. When perfusion pressure was changed stepwise between 60 and 200 mmHg, the infusion of acetylcholine or carbachol caused no impairment of autoregulation. It is concluded that autoregulation is independent of muscarinic stimulation of vascular smooth muscle in the kidney.     

吸烟对终末期肾病患者全段甲状旁腺激素与左心室重塑的影响

目的研究并分析吸烟对终末期肾病患者全段甲状旁腺激素（ierH）水平的影响以及与左心室重塑的关系。方法根据吸烟情况将139例慢性肾小球肾炎终末期肾病非透析患者分组,测定各组的iPTH及其他临床化验指标,并计算各组左心室质量指数（LVMI）。分析吸烟对ipTH的影响以及与LVMI的相关性。结果吸烟组iPTH高于不吸烟组,重度吸烟组iPTH高于轻度吸烟组,吸烟与iPTH独立正相关,且iPTH随着吸烟量增加而升高,呈剂量依赖关系;有左心室肥厚组iPTH高于无左心室肥厚组,iPTH与LVMI独立正相关。结论血iPTH指标的提升是终末期肾病吸烟患者高发左心室肥厚症状的关键因素,值得临床重视。