<i>Renal Responses to Exercise, Heat and Dehydration</i>

Smith, J. H.; Robinson, Sarah; Pearcy, M.

doi:10.1152/jappl.1952.4.8.659

Cited by 78 publications

(38 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fall in ERPF observed with moderate exercise in normals is comparable to that seen in previous studies [1][2][3]5,14]. It has been suggested that this observation may be an artefact due to a change in the distribution of intra-renal blood flow causing a fall in the renal extrac tion ratio of PAH on exertion, but a careful study in pigs (which have similar renovascular physiology) has de monstrated that intrarenal blood flow distribution re mains unchanged on exertion [15].…”

Section: Discussionsupporting

confidence: 81%

Effects of Exercise on Renal Function in Patients with Moderate Impairment of Renal Function Compared to Normal Men

Taverner

Craig²,

Mackay³

et al. 1991

Nephron

View full text Add to dashboard Cite

The renal excretory and haemodynamic responses to sustained moderate exertion were investigated in normotensive humans with impaired renal function and normal volunteers. The heart rate increase with exercise was similar in each group. Subjects with impaired renal function showed a significant fall in glomerular filtration rate on exertion, while normals did not. In the presence of renal disease, urine osmolality did not rise with exertion, although it rose markedly in the normal group. Free water clearance became negative after exercise in the normal group only. The diseased kidney is unable to maintain glomerular filtration rate or conserve water under the stress of exertion as well as the normal kidney.

show abstract

Section: Discussionsupporting

confidence: 81%

Effects of Exercise on Renal Function in Patients with Moderate Impairment of Renal Function Compared to Normal Men

Taverner

Craig²,

Mackay³

et al. 1991

Nephron

View full text Add to dashboard Cite

show abstract

“…14, the decrease in flow was proportional to the severity of exercise, with more than a 20% decrease at a heart rate of 100 beats/ min. Smith et al (1952) observed a similar decrease at 25°C during exercise, and with the addition of heat, the decrease in RPF was only slightly more than that at room temperature (Fig. 15).…”

Section: Cardiovascular Physiology: Renal Blood Flowsupporting

confidence: 54%

“…Effect of exercise on renal plasma flow (% change) during heat exposure as a function of heart rate. Observed data were taken from the literature (Smith et al 1952). …”

Section: Fig 12mentioning

confidence: 99%

Simulation of differential drug pharmacokinetics under heat and exercise stress using a physiologically based pharmacokinetic modeling approach

Sidhu

Peng

Cheung

et al. 2011

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

Under extreme conditions of heat exposure and exercise stress, the human body undergoes major physiological changes. Perturbations in organ blood flows, gastrointestinal properties, and vascular physiology may impact the body's ability to absorb, distribute, and eliminate drugs. Clinical studies on the effect of these stressors on drug pharmacokinetics demonstrate that the likelihood of pharmacokinetic alteration is dependent on drug properties and the intensity of the stressor. The objectives of this study were to use literature data to quantify the correlation between exercise and heat exposure intensity to changing physiological parameters and further, to use this information for the parameterization of a whole-body, physiologically based pharmacokinetic model for the purposes of determining those drug properties most likely to demonstrate altered drug pharmacokinetics under stress. Cardiac output and most organ blood flows were correlated with heart rate using regression analysis. Other altered parameters included hematocrit and intravascular albumin concentration. Pharmacokinetic simulations of intravenous and oral administration of hypothetical drugs with either a low or high value of lipophilicity, unbound fraction in plasma, and unbound intrinsic hepatic clearance demonstrated that the area under the curve of those drugs with a high unbound intrinsic clearance was most affected (up to a 130% increase) following intravenous administration, whereas following oral administration, pharmacokinetic changes were smaller (<40% increase in area under the curve) for all hypothetical compounds. A midazolam physiologically based pharmacokinetic model was also used to demonstrate that simulated changes in pharmacokinetic parameters under exercise and heat stress were generally consistent with those reported in the literature.

show abstract

“…Ro 03-8799 is eliminated rapidly not only by urinary excretion but also by metabolic N-oxidation in both mice (Walton et al, 1985) and man (Roberts et al, 1986;Allen et al, 1984). The (Smith et al, 1952), an effect mainly attributed to decreased renal blood flow (Radigan & Robinson, 1950 Reinhold et al, 1985). Lot alter adriamycin WBH may also decrease tissue pH through stimulation of /2a.…”

Section: Discussionmentioning

confidence: 99%

The effects of whole body hyperthermia on the pharmacokinetics and toxicity of the basic 2-nitroimidazole radiosensitizer Ro 03-8799 in mice

Walton¹,

Bleehen²,

Workman³

1987

Br J Cancer

View full text Add to dashboard Cite

Summary We have investigated the effects of 50 min whole-body hyperthermia (WBH; 15 min equilibration followed by 41°C for 35min) on the toxicity and pharmacokinetics of the radiosensitizer Ro 03-8799 in mice.WBH markedly reduced Ro 03-8799 LDSO,7d from 779 to 259 igg-1 (P<0.001). Pharmacokinetics were studied at 175 pgg 1 (-0.6WBHLDSO57d) with and without heat and 437,igg-1 (-0.6 control LDSO/7d) without heat. WBH increased Ro 03-8799 plasma concentrations and prolonged its elimination t112 by 26% (P<0.01). Total plasma area under the curve (AUC,,_-) was increased by 22%. but was still <50% of the unheated high-dose value. Ro 03-8799 concentrated 300-400% in tumour and brain relative to plasma. Absolute tumour and brain levels were unaltered by WBH, giving reduced tissue/plasma ratios. WBH greatly inhibited glomerular filtration (51Cr EDTA clearance) during heating, contributing to the increased plasma Ro 03-8799 concentrations. WBH increased peak plasma concentrations of the Ro 03-8799 N-oxide metabolite Ro 31-0313 by 61%, and the fl-phase AUC of i.v. administered Ro 31-0313 by 36%. Since Ro 31-0313 levels were increased to a greater extent after Ro 03-8799 and WBH than Ro 31-0313 and WBH, WBH must both increase metabolite production and decrease its plasma clearance. WBH had no effect on Ro 31-0313 tumour concentrations or its exclusion from brain. These complex effects of WBH on Ro 03-8799 pharmacokinetics may contribute to the enhanced toxicity, possibly through hyperthermia-stimulated bioreductive drug activation, but do not wholly explain it.The curability of many tumours by radiotherapy may be limited by the presence of radioresistant hypoxic tumour cells. Electron affinic compounds such as the nitroimidazoles act as hypoxic cell radiosensitizers and are also preferentially cytotoxic towards these cells (Adams et al., 1976). Hyperthermia enhances the tumour cytotoxicity of the 2-nitroimidazole radiosensitizer misonidazole (MISO; 1 -(2-nitroimidazol-1 -yl)-3-methoxy-2-propanol) both in vitro (Stratford and Adams, 1977) and in vivo (Bleehen et al., 1977;George et al., 1977) but also increases its acute lethality in mice (Overgaard, 1979).MISO is likely to produce sub-optimal radiosensitization in man because dose-limiting neurotoxicity limits achievable tumour concentrations (see Workman, 1983). Recent studies have shown that 2-nitroimidazoles substituted with basic side chains are more potent radiosensitizers than MISO in vitro (Smithen et al., 1980), with shorter half-lives and hence lower tissue exposures in vivo (Williams et al., 1982 Materials and methodsMice and tumours Adult C3H/He mice were obtained from our own breeding colony and from Olac Ltd (Bicester, UK). Males were used in most experiments but females were used occasionally. Mice were allowed food (PRD nuts; Labsure, Poole, Dorset, UK) and water ad lib, and were used at 25-35 g body weight.The KHT sarcoma was grown in the gastrocnemius muscle of the hind leg as previously described (Twentyman et al., 1979). Mice were treated bearing tumours...

show abstract

Renal Responses to Exercise, Heat and Dehydration

Cited by 78 publications

References 0 publications

Effects of Exercise on Renal Function in Patients with Moderate Impairment of Renal Function Compared to Normal Men

Effects of Exercise on Renal Function in Patients with Moderate Impairment of Renal Function Compared to Normal Men

Simulation of differential drug pharmacokinetics under heat and exercise stress using a physiologically based pharmacokinetic modeling approach

The effects of whole body hyperthermia on the pharmacokinetics and toxicity of the basic 2-nitroimidazole radiosensitizer Ro 03-8799 in mice

Contact Info

Product

Resources

About