PubMed Health⌕ Search

Biomedical subjects

M MacLaughlin

Publications and source records attributed to M MacLaughlin.

13 recordsLinked to original sources
PubMed2001

Intrarenal renin-angiotensin system contributes to tubular acidification adaptation following uninephrectomy.

BACKGROUND/AIMS: Reduction in renal mass by uninephrectomy induces a functional compensation in the remnant kidney. The activity of the angiotensin-converting enzyme (ACE) as well as renin mRNA in the proximal convoluted tubule (PCT) of uninephrectomized (UNx) rats increases. The aim of this work was to determine whether the increased activity of the local renin-angiotensin system (RAS) participates in the adaptation of renal function after uninephrectomy. METHOD: We utilized normal two-kidney (2K) and 3-week UNx rats to study the activity of the ACE in vesicles obtained from luminal membranes of proximal tubular cells and the acidification kinectics in PCTs using micropuncture techniques. RESULTS: The converting enzyme activity was significantly larger in UNx (5.87+/-0.69 nmol x min(-1) x mg protein(-1)) than in 2K rats (2.43+/-0.13 nmol x min(-1) x mg protein(-1); p<0.05). The acidification rate constant (kappa) in PCT of 2K rats was 0.18+/-0.02 s(-1) and in UNx rats 0.30+/-0.04 s(-1) (p<0.001). In UNx rats, microperfusion with 10(-5) M ramipril or 10(-5) M losartan decreased kappa to 0.19+/-0.02 and 0.18+/-0.02 s(-1), respectively, but had no effect on 2K rats. Luminal steady-state pH (pH(infinity)) was the same in 2K and UNx rats, and was not modified by addition of 10(-5) M ramipril or 10(-5) M losartan in both groups. The proximal H(+) flux (J(H(+))), calculated from pH(infinity) and kappa, was 1.12 nmol x cm(-2) x s(-1) in 2K rats and, 1.77 nmol. cm(-2). s(-1) in UNx rats (p<0.001). In 2K rats, this value was not changed by 10(-5) M ramipril or 10(-5) M losartan, but in UNx rats J(H(+)) decreased 25 and 30% with ramipril or losartan, respectively (p<0.001). CONCLUSIONS: These data suggest that the increase in the local RAS activity could be an adaptive change that contributes to maintain the homeostasis of body fluids after uninephrectomy.

Acids↗
PubMed2000

Is dependence on one drug associated with dependence on other drugs? The cases of alcohol, caffeine and nicotine.

Several studies have correlated the use of one drug with that of another drug; however, whether dependence on one drug is associated with dependence on another drug, independent of any use/use association, is unclear. We asked 196 randomly-selected subjects the DSM-IV criteria for dependence as applied to alcohol, caffeine, and nicotine. Among ever users, the severity of alcohol vs nicotine dependence and alcohol vs caffeine dependence was related, but this relationship was weak (r = .22 & .31). Nicotine and caffeine dependence were not correlated. These results fail to confirm theories of commonality that hypothesize dependence on one drug predisposes to dependence on another drug.

Adult↗
PubMed1999

Effect of smoking abstinence on the subjective effects of caffeine.

Abstinence from smoking increases blood levels of caffeine and may potentiate the ability of caffeine to increase anxiety, insomnia, etc., during smoking cessation. The present study tested this hypothesis using a wider range of abstinence levels (0, 36 and 84 h), caffeine doses (0, 200 and 400 mg) and subjective effects (31 measures) than prior studies. Fourteen participants were studied using a randomized, within-subjects, double-blind design. Participants were tested on 31 subjective variables, two performance and two physiological variables on five occasions over the 3 h following dosing. Although abstinence and caffeine produced their prototypic effects, only one of the 35 interactions tested was significant and the magnitude of this interaction was small. Although our statistical power was limited, we conclude abstinence from smoking does not change the subjective effects of caffeine in the first days of abstinence. These results and those of prior studies suggest smokers who are trying to stop smoking do not need to change their caffeine intake.

Adolescent↗
PubMed1998

Role of kinins in the renoprotective effect of angiotensin-converting enzyme inhibitors in experimental chronic renal failure.

The aim of this study was to investigate whether the renoprotective effect of angiotensin-converting enzyme inhibitors (ACEIs) following 5/6 renal mass reduction is due in part to the potentiation of kinins. Three groups of rats with 5/6 renal mass reduction were studied during the 14 weeks following surgery. One group received no therapy (control); the second group was treated from the beginning with the ACEI ramipril (1 mg/kg/day) added to the drinking water, and the last group received ramipril plus a beta2-bradykinin antagonist, HOE 140 (500 microg/kg/day) via osmotic minipumps. Plasma creatinine did not change in any group during the study. Urinary protein excretion rose in the controls from 9.18+/-1.6 to 45.0+/-5.6 mg/24 h at the end of the study. In ramipril group proteinuria was prevented (initial 7.5+/-1.0 and final 8.6+/-0.8 mg/24h). The effect of ramipril was abolished by HOE 140 (initial 11.6+/-2.0 and final 38.9+/-11 mg/ 24 h). The systolic blood pressure of the controls increased from 106+/-2 to 144+/-5 mm Hg at the 14th week. Ramipril abolished the increase in systolic blood pressure. The effect of ramipril was reverted by HOE 140 (initial 108+/-2 and final 140+/-9 mmHg). Control rats had more severe histopathologic changes. Those animals receiving ramipril + HOE 140 displayed less severe glomerular changes, while rats treated only with ramipril had mild alterations. Thus the glomerular injury score was 2.11+/-0.32 for controls, 1.53+/-0.52 for rats treated with ramipril + HOE 140, and 0.06+/-0.04 for rats treated only with ramipril. The glomerular area was 20,886+/-1,410, 19,693+/-2,200 and 14,352+/-3,200 microm2, respectively, for the 3 groups. These results suggest that the protective effect of ACEIs in the development of chronic renal failure is partially mediated by kinins.

Administration, Oral↗
PubMed1997

Adenosine activates mesangial cell proliferation.

This study investigates the proliferative effect of adenosine (ADO) in cultured mesangial cells, and the possible mediation of A1 and/or A2 receptors in this proliferative effect of ADO. ADO (10(-5) M) induced a significant increase in the [3H]thymidine incorporation into DNA with respect to quiescent cells. This increase was similar to that obtained with the ADO A1 receptor agonist, R-PIA (10(-5) M), and with the ADO A2 receptor agonist, NECA (10(-5) M). Theophylline (10(-4) M), and ADO receptors inhibitor, completely inhibits the ADO-induced proliferation. The combinations NECA + A2 receptor antagonist, PD 116,948 (AT1, 10(-6) M) and PIA + A2 receptor antagonists, PD 115,199 (AT2, 10(-2) M) did not induce any significant difference with respect to cells maintained in control conditions. These findings demonstrate the proliferative effect of ADO in cultured mesangial cells, and that this effect is not specific to either of A1 or A2 receptors activation.

Adenosine↗
PubMed1996

Converting enzyme inhibition and renal function of conscious uninephrectomized rats [correction of enzyme].

We studied the effect of a Converting Enzyme Inhibitor, Captopril, on renal function of conscious, chronically instrumented uninephrectomized rats three weeks after surgery and normal two kidney rats. Captopril increased glomerular filtration rate from 9.28 +/- 0.50 to 14.23 +/- 1.07 ml/min.kg and effective renal plasma flow from 31.6 +/- 2.4 to 45.8 +/- 3.7 ml/min.kg in two kidney rats. Glomerular filtration rate and effective renal plasma flow of uninephrectomized rats did not change after acute converting enzyme inhibition (from 6.96 +/- 0.61 to 7.16 +/- 0.39 and 24.5 +/- 2.2 to 27.9 +/- 1.5 ml/min.kg respectively). Plasma renin activity was lower in uninephrectomized rats (0.72 +/- 0.15 ng AngI/ml.h) than in intact rats (1.41 +/- 0.20 ng AngI/ml.h). Acute converting enzyme inhibition increased urinary sodium excretion, fractional sodium excretion and plasma renin activity in both, two kidney and uninephrectomized rats without changes of mean arterial pressure. Present data suggest that the Angiotensin II does not participate in the control of glomerular filtration rate and effective renal plasma flow of uninephrectomized rats but it is implicated in the control of Na homeostasis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Evolution of experimental mild and severe chronic renal failure in the rat. Mathematical models.

Two degrees of renal insufficiency were obtained in female Wistar rats, one mild (M) and the other severe (S) by surgical resection of 2/3 or 3/4 of one kidney, followed by contralateral nephrectomy. The serum creatinine concentration (Cr) s was evaluated as an index of renal function and followed in the two mentioned groups under a normal protein diet and in "S" also under a low protein diet. The evolution was assessed by two functions of time: 1/(Cr) s and log e (Cr) s. Several differences between M and S were detected. In M a smaller initial and maximal increase in (Cr) s than in S followed by a plateau was observed; in S a decrease in (Cr) s posterior to the initial increase was detected attributed to hyperfiltration followed by a sustained increment. The lowering of protein content in the diet caused a decrement in (Cr) s. In both groups a better adjustment with the logarithmic than with the inverse function was obtained, although poorer in S rats owing to a larger variability. In order to look for a mathematical link between inulin clearance (Cl In) and (Cr) s, the relationship between Cl In vs. 1/(Cr) s, and log e Cl In vs. log e (Cr) s was studied in normal and in rats in renal insufficiency. By regression analysis we found a good adjustment with both functions from 0.58 to 1.60 mg % (Cr) s.

Animals↗
PubMed1989

Impairment of the renal tubular acidification kinetics by lithium.

We studied the kinetics of HCO3- reabsorption in the middle proximal (MPT) and distal convoluted tubules (DCT) by measuring continuously intratubular pH with Sb-microelectrodes in stopped-flow microperfusion (HCO3-, 30 mM Ringer) experiments. Male Wistar rats (240-280 g) were injected ip with LiCl (4 mEq kg-1 day-1) for 4 days (Li) and were compared to controls (C). Steady-state pH increased in MPT from 6.64 +/- 0.02 (57) to 6.89 +/- 0.02 (45), mean +/- SEM (number of measurements) on tissue from 13 rats in each group, and from 6.87 +/- 0.05 (30) to 7.08 +/- 0.01 (63) in DCT. HCO3- reabsorption decreased from 1.32 +/- 0.08 (57) to 0.96 +/- 0.04 (45) nmol cm-2 s-1 in MPT and from 0.85 +/- 0.07 (30) to 0.45 +/- 0.04 (63) in DCT. These data indicate that lithium affected the acidification mechanism in MPT and DCT, probably through an impairment of the Na(+)-H+ antiport in both tubular segments.

Animals↗
PubMed1985

Verapamil effect on renal function of normotensive and hypertensive rats.

The effect of verapamil, a Ca++ antagonist drug, on renal function and proximal fluid reabsorption in normal and hypertensive (GII) rats was studied. During intravenous infusion of verapamil, mean arterial pressure (MAP) fell significantly in both groups, 23% more in hypertensive than in normotensive rats. Glomerular filtration rate (GFR) was significantly higher in hypertensive rats and also increased significantly in this group during verapamil infusion. Effective renal plasma flow (ERPF) was similar in both groups and did not change significantly during verapamil infusion. The increase in urine flow, Na+ and Ca++ excretion was higher in hypertensive than in normotensive rats during verapamil infusion. When 10(-5) M verapamil was added to the luminal perfusate of proximal tubules, fluid reabsorption was reduced to 64% in normotensive and to 42% in hypertensive rats. When added to capillary perfusate, fluid reabsorption was almost completely but reversibly inhibited (92% in normotensive and 83% in hypertensive rats). Our findings indicate a direct effect of verapamil on renal Na+ and possibly also on Ca++ reabsorption, suggesting involvement of the Na+-Ca++ countertransport system. The greater effect of verapamil on Na+ excretion in hypertensive rats was not due to increased action on proximal Na+ reabsorption.

Absorption↗
PubMedDate not supplied

Proximal Na+, fluid and HCO3- reabsorption in uninephrectomized rats after a saline load.

We studied the effect of a saline load on proximal tubular Na+, fluid and HCO3- handling of control and uninephrectomized (UNx) rats. Glomerular filtration rate (GFR) was measured by inulin clearance, Na+ reabsorption in the proximal tubule by lithium clearance (CLi+), proximal tubule fluid reabsorption (Jv) by microperfusion with 14C inulin and proximal tubule HCO3- reabsorption (JHCO3-) by estimating pH of perfusate and collected fluid in vitro under CO2 equilibrated oil by means of Sb microelectrodes. No significant differences were found between control and UNx animals in baseline values of urine flow, GFR, fractional water and sodium excretion and blood and urine pH and pCO2, showing that renal function was compensated 4 weeks after UNx. On the other hand, UNx rats showed a significant increase in proximal tubule Jv and JHCO3-. After extracellular fluid volume expansion (EFVE) by infusion of HCO3- Ringer solution (0.1 ml/min) during 90-120 min, in both groups of animals hematocrit decreased by 15%, GFR remained unchanged and fractional Na+ and water excretion increased significantly. However, after EFVE Jv and JHCO3- decreased significantly in control rats but were not modified in UNx animals. Fractional proximal Na+ reabsorption as measured by CLi+ decreased in control rats after EFVE and was not altered in UNx rats. After EFVE the fall in fractional distal Na+ reabsorption was significantly higher in control than in UNx rats. The present results provide evidence that after a saline load the impaired natriuretic response in UNx rats could be attributed to an alteration in proximal and distal tubular Na+ and HCO3- handling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗