Differential Effects Of Hypoxia Research Articles

Differential effects of hypoxia on electrical and mechanical activities of isolated ventricular muscles from fetal and adult guinea-pigs

1. 1. Effects of hypoxia (95% N 2 + 5% CO 2) and cromakalim (30 μM) on mechanical and electrical activities of isolated ventricular muscles were examined in fetal and adult guinea-pigs. 2. 2. Hypoxia markedly reduced both the action potential duration (APD) and the contractile force (CF) in the adult, which was only partially restored by 10 μM glibenclamide, while it only slightly reduced CF with little affecting APD in the fetus. 3. 3. Cromakalim markedly reduced both APD and CF in both age groups similarly. 4. 4. Thus, we demonstrated that APD and CF of fetal ventricular muscles are resistant to hypoxia as compared with those of adult. This may be explained by difference in metabolic pathways rather than by lack of ATP-sensitive potassium channels.

P-215 - Differential effects of hypoxia on ligand binding properties of nicotinic and muscarinic acetylcholine receptors on cultured bovine adrenal chromaffin cells.

P-215 - Differential effects of hypoxia on ligand binding properties of nicotinic and muscarinic acetylcholine receptors on cultured bovine adrenal chromaffin cells.

Differential effects of hypoxia upon contractions evoked by potassium and noradrenaline in rabbit arteries in vitro.

1. A study has been made on isolated sections of rabbit femoral, renal and saphenous arteries of the effects of graded hypoxia (reducing bath PO2 from 110 mmHg, normoxia, to 55, 23 and 6 mmHg) upon contractile responses evoked by noradrenaline (NA) and KCl to 80% of maximum. 2. Potassium-evoked contractions were not affected by moderate hypoxia but were reduced in all vessels to 70-80% of the control response in normoxia, by exposure to either PO2 23 or 6 mmHg. Potassium-evoked contractions were virtually abolished by Ca2(+)-free Krebs solution and greatly reduced by verapamil (10 microM), indicating that they relied upon influx of extracellular Ca2+. 3. By contrast, NA-evoked contractions were reduced in a graded fashion in all vessels by exposure to graded levels of hypoxia and at PO2 6 mmHg they were significantly more reduced than K(+)-evoked contractions. Noradrenaline-evoked contractions of femoral arteries were most affected, being reduced to 80% of control at PO2 55 mmHg, and to 28% and 6% of control at PO2 23 and 6 mmHg respectively. Contractions in renal arteries were least affected, being reduced to only 47% of control at PO2 6 mmHg. 4. Noradrenaline-evoked contractions were reduced, but not abolished, in Ca2(+)-free Krebs solution. In normoxia, they reached 42%, 35% and 25% of control responses in the presence of Ca2+ in femoral, renal and saphenous arteries respectively. The Ca2(+)-free responses of the femoral and saphenous arteries were significantly different, indicating that the femoral arteries were least dependent and saphenous most dependent on influx of extracellular Ca2+ for contraction. 5. Contractions evoked by NA in Ca2(+)-free Krebs solution were not significantly affected by PO2 55 mmHg. Those evoked in saphenous arteries were not affected by more severe hypoxia, but in renal arteries they were significantly reduced at PO2 23 mmHg, while in femoral arteries they were significantly reduced both at PO2 23 and at PO2 6 mmHg. 6. Verapamil produced changes similar to Ca2+ withdrawal. Contractions evoked by NA in the presence of verapamil were affected by hypoxia in a similar way to those evoked in the absence of Ca2+. 7. These results indicate that the inhibition of contraction induced by hypoxia is not simply dependent upon inhibition of Ca2+ influx. Instead, we propose that receptor-operated rather than voltage-operated processes are particularly vulnerable, there being inhibition of the components of contraction which are dependent on receptor-operated Ca2+ influx and release of intracellular Ca2+.

Differential effects of hypoxia on sleep of warm- and cold-acclimated rats.

We studied the effect of different levels of hypoxia (10, 12 or 13, 15, and 18% O2) on the sleep-waking pattern (SWP) and the maximum-minimum core temperature of warm-acclimated (WA) and cold-acclimated (CA) rats at their neutral temperature, 29 degrees C. Whereas the SWP of WA rats showed a trend toward increasing disruption as the degree of hypoxia increased, CA rats exhibited no such trend. The effect was chiefly on the frequency of state changes and less on epoch durations. The SWP of WA rats was more vulnerable to hypoxia than that of CA rats. Maximum and minimum body temperatures of WA and CA rats were not significantly affected by O2 lack down to 10% inspired O2. We conclude that in the rat 1) hypoxia primarily affects the neural mechanism that governs the frequency of changes in sleep-waking states; 2) the extent of alterations in SWP's depends on the ambient temperature to which the rats are acclimated; and 3) hypoxia does not significantly affect deep body temperature at the animal's neutral temperature.

Differential effects of hypoxia on the disposition of propranolol and sodium taurocholate by the isolated perfused rat liver.

Although the adverse effect of hypoxia on drug metabolism is well documented in subcellular systems, its effect on drug clearance by the intact liver has not been defined. This study was undertaken in the isolated perfused rat liver to examine the effects of acute hypoxia on the hepatic elimination of two highly cleared substances--propranolol and sodium taurocholate. Hypoxia was established by equilibrating the perfusate with 100% nitrogen rather than 100% oxygen. This led to a fall in portal vein pO2 from 300 to 30 mm Hg, and a 10-fold rise in hepatic venous lactate:pyruvate ratio, indicating a profound alteration in hepatic cellular redox state. In bolus dose studies, propranolol uptake was unimpaired by hypoxia, with a monoexponential decline in perfusate concentrations from 2,000 to 30 ng per ml, (t1/2 uptake = 2.5 min). After 20 min of hypoxia, perfusate propranolol concentrations rose from 30 to 80 ng per ml, indicating release of propranolol from liver back into the perfusate. Reoxygenation of perfusate restored hepatic extraction of propranolol to normal (t1/2 uptake = 2.37 +/- 0.19 min vs. 2.55 +/- 0.60 min p greater than 0.1) such that perfusate concentrations were undetectable by 30 min. In steady-state studies, perfusate propranolol concentrations rose from 1.55 +/- 0.50 to 4.08 +/- 1.47 micrograms per ml (p less than 0.005), after 1 hr of hypoxia indicating a change in propranolol clearance from 15 ml per min to less than 6 ml per min. Reoxygenation resulted in a fall in perfusate propranolol concentrations towards control values (2.78 +/- 1.13 vs. 1.80 +/- 0.41 micrograms per ml, p greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hypoxia and altered K 0 on the membrane potential of rabbit ventricle

The upstroke of the ventricular action potential in the rabbit consits of two depolarizing components with different rates of rise. The effects of hypoxia on the resting potential (RP); the upstroke phases (I and II) and the maximum rate of rise of phase I (V̇ max) were studied at different external K concentrations (K 0). Perfused hearts were submitted to N 2-equilibrated media containing 1.5 to 10 m m K 0. Exposure of oxygenated hearts to different K 0 changed the regenerative response from a fast rising action potential at 1.5 m m K 0 to a depressed fast response at 7.5 and 10 m m K 0. Hypoxia decreased the action potential amplitude (APA) at all K concentrations. In K 0 ≤ 5 m m the reduction of APA was due to a decrease in the amplitude of phase II of the upstroke but the maximum rate of rise (V̇ max) did not change. In contrast, phase I of the upstroke was markedly depressed by hypoxia in high K 0, but phase II was unmodified and its V̇ max compared well with values reported for other normoxic cardiac cells. Hyperkalemia per se did not slow conduction during normoxia but increased conduction time in hypoxia. The resting potential of hypoxic cells was closer to the K equilibrium potential than in the control. The RP v. K 0 K i relation suggested that electrogenic Na extrusion persists in hypoxia. The electrogenic fraction of the resting potential as determined from pump inhibition with 10 −4 m ouabain amounted to −6 mV. Our results did not indicate whether the differential effects of hypoxia on the upstroke components were potential dependent or were related to direct effects of K + on the ionic currents that determine the action potential. The persistence of phase II during hypoxia in partly depolarized cells may assure the maintenance of propagated electrical activity under conditions that are likely to be encountered in vitro during cardiac ischemia.

PROCEEDINGS OF THE AUSTRALASIAN SOCIETY OF CLINICAL AND EXPERIMENTAL PHARMACOLOGISTS

PROCEEDINGS OF THE AUSTRALASIAN SOCIETY OF CLINICAL AND EXPERIMENTAL PHARMACOLOGISTS