摘要:

SUMMARY1. It is a central thesis of this review that in clinical and experimental pharmacology and physiology the goal of statistical analysis should be to minimize the risk of making any false–positive inferences from the results of an experiment (experimentwise Type I error).2. It is common in clinical and experimental pharmacology and physiology for the effects of several treatments to be tested within a single experiment. Specific intercomparisons of these several effects, made in a pairwise or more complex fashion, inflates the risk of making false–positive inferences unless special statistical procedures are used.3. A number of multiple comparison procedures is described and their ability to control experimentwise Type I error is evaluated critically.4. When only a few (<5) of all possible pairwise or more complex comparisons are made between treatment groups, the Dunn‐Šdák procedure provides maximum protection against excessive experimentwise Type I error and is very convenient to use.5. When a control group is compared with all other treatment groups in a pairwise fashion, especially when the number of groups is large, the Dunnett procedure is more powerful than the Dunn‐Šidák.6. If investigators insist on making all possible pairwise comparisons among treatment groups, the Tukey‐Kramer procedure provides maximum protection against false‐positive inferences but inflates the Type II error rate. If it is especially important to avoid Type II error then the more complicated, stepwise procedures of the Ryan‐Peritz‐Welsch variety s

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01468.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. To determine the effect of chloride ion on the development of hypertension and the incidence of cerebral lesions in stroke‐prone spontaneously hypertensive rats (SHRSP), groups of 10 rats were administered chronically with either 171 mmol/L sodium chloride or equimolar sodium provided as sodium citrate in the drinking water from the age of 12 weeks.2. The life span was significantly extended in SHRSP given sodium citrate (336 ± 28vs246 ± 26 days, mean ± s.e.m.,P<0.05) but their development of hypertension was not different from SHRSP given sodium chloride.3. In order to determine the role of calcium homeostasis, calcium in urine was collected. Urinary calcium in SHRSP given sodium citrate was significantly decreased (1.0 ± 0.12vs1.8 ± 0.18 mg/ 24 h urine,P<0.05).4. If the normal life span is 320 ± 35 days, this suggests that chloride ion ingested with sodium accelerates the development of cerebrovascular diseases, and that increased urinary calcium excretion may be related to this adverse chloride effect on the development of hypertension i

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01469.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. Effects of administration ofNG‐nitro‐L‐arginine (NO2Arg), a guanidino nitroarginine derivative, for 1 week on blood pressure and some vascular responses of rats were studied.2. A significant rise of the systolic blood pressure was observed after the administration of NO2Arg with food (0.023% in weight, about 2.8 mg of NO2Arg per rat per day). Relaxation by acetylcholine decreased markedly in ring preparations of the thoracic aorta of NO2Arg‐treated rats. However, glyceryltrinitrate‐induced relaxation was not reduced after NO2Arg administration, suggesting that NO2Arg administration specifically inhibited endothelium‐dependent relaxation.3. An increase of blood pressure may be because oral administration of NO2Arg inhibited endothelium‐dependent relaxationin vivosuggesting that the release of EDRF is important in physiological control of b

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01470.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. The α2‐adrenoceptor agonist clonidine elicits centrally mediated effects through an interaction with both α2‐adrenoceptors and imidazoline binding sites.2. We selected a new oxazoline derivative, S 8350, which competes with [3H]‐yohimbine for binding to cerebral α2‐adrenoceptors (IC50, 67 ± 17 nmol/L) and displays a higher affinity (35‐fold) for α2‐ than for α1‐adrenoceptors.3. As observed for clonidine, intravenous (i.v.) administration of S 8350 resulted in a brief pressor effect followed by a prolonged hypotension. When S 8350 was administered i.v. to spinally pithed rats, only a rise in blood pressure was observed.4. In order to discriminate the cardiovascular effects related to the central imidazoline receptor or α2‐adrenoceptor activation, the effects of intracisternal (i.c.) administration of clonidine and S 8350 were investigated in the rat.5. In the anaesthetized rat, both clonidine and S 8350 displayed a profound central (i.c. route) hypotensive effect associated with a bradycardia.6. The cardiovascular effects of S 8350 were abolished by the central administration of the selective α2‐adrenoceptor antagonist rauwolscine. Conversely, rauwolscine completely prevented bradycardia but it induced only a partial reversion of the hypotension elicited by clonidine.7. These results suggest that central α2‐adrenoceptors are responsible for hypotension and bradycardia while imidazoline binding sites do not apparently cont

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01471.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. Medullipin I (Med I) is a hormone extracted from renal papillae and its renomedullary interstitial cells (RIC). Med I is stimulated by elevation of the renal artery perfusion pressure.2. When isolated normal rat kidneys were perfused either with oxygenated blood or with 5% albumin bubbled with O2at elevated perfusion pressures, Med I appeared to be secreted into the renal venous effluent (RVE). Addition of Tween 20, treatment of the assay rat with SKF 525A, inhibitor of cytochrome P‐450 and removal of the liver from the systemic circulation prevented vasodepression of both the RVE and extracted Med I. The lipid in the RVE gave the same dose–response as extracted Med I.3. Lowering the renal artery perfusion pressure below normal inhibited the secretion of Med I. As the perfusion pressure was elevated Med I secretion appeared to increase.4. Previous observations and the present study support the view that the renin–angiotensin system and the Medullipin system are double feedback systems involved in blood pressure co

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01472.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. Stimulation of adult female rats with pregnant mare serum gonadotropin (PMSG) and human chorion gonadotropin (hCG) increased active plasma renin about two‐fold, but caused only a slight increase of plasma prorenin. The concentrations of active renin and prorenin in the ovaries, and active renin in the uterus all increased about two‐fold 2 days after stimulation with PMSG. The prorenin in the uterus was below detection in unstimulated rats and did not change consistently after PMSG.2. Active renin and prorenin in plasma were unchanged in relation to pregnancy, except for a slight decrease of prorenin in the third trimester. In the first and third trimester the concentration in the ovaries of active renin and prorenin was decreased to about one‐third of that in normal female rats. In contrast active renin in the uterus was increased about two‐fold in the first trimester, whereas prorenin did not change consistently.3. Our results confirm that gonadotropins and pregnancy affect the renin–angiotensin system in rats. However, the changes in the plasma seem to be much smaller than those previously reported in humans. Accordingly, our results do not support a systemic role of prorenin for reproduction i

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01473.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. The effects of reserpine treatment on the contents of catecholamines and opioid peptides have been studied in the rat hypothalamus and pituitary.2. Hypothalamic and pituitary catecholamines were drastically depleted following acute reserpine treatment.3. Reserpine treatment also resulted in a significant decrease in immunoactive met‐enkephalin content in both the hypothalamus (25%) and the anterior lobe (50%), but not in the neurointermediate lobe of the pituitary.4. No changes were observed in immunoactive β‐endorphin levels.5. These findings suggest that the met‐enkephalin contents in the hypothalamus and the anterior pituitary may be under catecholaminergic control.6. The lack of effect of acute reserpine treatment on immunoactive β‐endorphin contents might be due to the opposing effects of adrenergic and dopaminergic m

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01474.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. To evaluate and compare the effects of the calcium channel blockers, diltiazem and verapamil, on CNS modulation of blood pressure, unanaesthetized and unrestrained rats with catheters previously inserted into the lateral cerebral ventricle and femoral artery received intra‐cerebroventricular (i.c.v.) administration of diltiazem or verapamil, 10 or 50 μg/kg, or their diluent.2. Diltiazem, at both 10 and 50 μg/kg i.c.v., produced significant (P<0.05) decreases in systolic and diastolic blood pressure and heart rate. Verapamil, at 50 μg/kg but not at 10 μg/kg i.c.v., produced a significant (P<0.05) decrease in blood pressure, while both doses significantly (P<0.05) decreased heart rate.3. To examine the endogenous opioid systems as potential modulators of the effects of these calcium antagonists, the mu opioid antagonist naloxone, 20 μg/kg, was administered i.c.v. either before or after each calcium antagonist. Naloxone reversed and prevented the reduction in blood pressure produced by both agents. The decrease in heart rate produced by verapamil but not diltiazem was reversed by naloxone.4. The results suggest that: (1) calcium channels in neuron membranes in the CNS play a role in blood pressure regulation; (2) at least part of the blood pressure reduction produced by calcium blockers may be effected in the CNS; and (3) central opioid mechanisms modulate part of the action of the calcium antagonists verapamil and diltiazem on blood pr

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01475.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. The effect of tolerance to glyceryl trinitrate (GTN) on vasodilator and vasoconstrictor responses was examined in conscious rabbits and isolated rabbit aortic rings.2. In conscious rabbits, depressor responses to 5 min infusions of GTN (10–40 μg/kg per min intravenously (i.v.)), sodium nitroprusside (SNP, 5–20 μg/kg per min i.v.) and acetylcholine (ACh, 3–12 μg/kg per min i.v.) were examined before and after transdermal treatment with GTN (20 mg/48 h). GTN pretreatment significantly attenuated GTN‐induced depressor responses, indicating the development of tolerance, but did not affect the reductions in arterial pressure induced by SNP or ACh.3. Similarly, aortic rings taken from GTN pretreated rabbits exhibited tolerance to GTN but the relaxant responses to SNP or the calcium ionophore A23187 were not affected. In the aortic rings from GTN‐tolerant rabbits contractile responses to serotonin or the thromboxane‐mimetic U46619 were significantly attenuated, in contrast to the responses to the α1‐adrenoceptor agonist phenylephrine (PE) which were significantly enhanced.4. Similarly, in conscious rabbits, PE‐induced increases in arterial pressure and hindlimb vascular resistance were significantly enhanced by GTN pretreatment but the responses to the α2‐adrenoceptor agonist BHT 920 were unaffected.5. In conclusion, tolerance to GTN does not affect endothelium‐dependent vasodilatation but does cause a selective enhancement of α1‐ but not α2‐adrenoce

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01476.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. Atrial natriuretic peptide (ANP) is degraded by neutral metalloendopeptidase (NEP) (EC 3.4.24.11) and the kidney is a major site of ANP clearance.2. The regional distribution of NEP in the rat kidney was investigated.3. The activity of NEP, measured with an enzymatic fluorimetric method employingN‐dansyl‐D‐alanyl‐glycyl‐L‐4‐nitrophenylalanyl‐glycine as a synthetic substrate, was 18 times and eight times higher in the outer stripe of the medulla and inner cortex than in the outer cortex (OC).4. Low concentrations of NEP were found in the OC, inner stripe and inner medulla.5. NEP activity in the rat kidney was inhibited by the specific NEP inhibitors (SCH39370, phosphoramidon and thiorphan) at micromolar concentrations.6. The present result suggests that degradation of ANP by NEP occurs mainly in the proximal tubules of the juxtamedullary nephrons, rather than cortical nephrons, and that the convoluted tubule in the OC is not a major site of location of NEP.7. The relationship between NEP activities in the kidneyin vitroand plasma clearance of ANPin vivoremains

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01477.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY