Non-stressed State Research Articles

Development of stress-induced gastric lesions involves central adenosine A 1-receptor stimulation

When rats were exposed to immobilization stress for 1–12 h, gastric lesions did not occur at 1–6 h of immobilization. Exogenous adenosine increased stress-induced gastric lesions, and dipyridamole, a blocker of adenosine uptake, potentiated the action of adenosine. The selective adenosine A 1-receptor stimulants N 6-cyclohexyl adenosine (CHA) and N 6-( l-phenylisopropyl) adenosine- l-PIA) produced gastric lesions even in non-stressed state and markedly potentiated in dose- and time-dependent manner in stressed state. The stimulatory effect of N 6-( d-phenylisopropyl) adenosine ( d-PIA) on ulceration was weaker than that of CHA or l-PIA. Furthermore, intracerebral ventricular (i.c.v.) injection of adenosine or adenosine analogues produced the most rapid and most potent exacerbation of stress-induced gastric lesions relative to those induced with subcutaneous (s.c.) injection. The stress lesions enhanced by CHA were not affected by phentolamine, yohimbine, prazosin, naloxone and cholecystokinin (CCK8) but were inhibited by caffeine, clonidine, morphine and β-endorphin. The inhibitory effect of clonidine was not antagonized by yohimbine or prazosin. The inhibition by morphine was selectively antagonized by exogenous CCK8 as well as naloxone. These results suggest that endogenous adenosine is tonically active in stress lesion formation which is modulated by opiate systems. Clonidine as well as caffeine may function as a purinoceptor antagonist, and it seems unlikely that the inhibitor effect of clonidine on stress ulcer is due to activation of α-adrenoceptors.

Differential effects of morphine on core temperature in stressed and non-stressed rats

The effects of morphine on body temperature were studied in rats in two different states — stressed and non-stressed. Morphine injected subcutaneously (s.c.) produced a dual action on body temperature in non-stressed rats. Hyperthermia occurred at lower doses (2.5–10 mg/kg) while hypothermia was produced with a higher dose (20 mg/kg). Both of these effects of morphine were reversed by naloxene (0.1–5.0 mg/kg). Stressing the rats (immobilization with wire mesh) produced slight hypothermia which was markedly potentiated by morphine (5–20 mg/kg) in a dose-dependent manner. Enhancement of hypothermia by morphine in the stressed animals was antagonized by pretreatment with naloxone (0.1–5.0 mg/kg). When rats were treated with morphine (10 mg/kg) 1 h before stress, and were then exposed to immobilization stress, the hyperthermia exhibited in the non-stressed state changed to hypothermia in the stressed state. When the rats which were treated with morphine and then stressed for 1 h were released from stress, the hypothermia observed in the stressed state progressively changed to hyperthermia. Furthermore, these morphine effects, i.e. hyper- and hypothermia in the non-stressed and stressed states, respectively, were reversed but not eliminated by naloxone. These results suggest that the effects of morphine on core temperature in rats are altered depending upon the state of the animals. That is, morphine appears to have a dual action, hyperthemia in the non-stressed state and hypothermia in the stressed state. It as also appears that these actions are mediated via opiate receptors.

Physiological effects of hypervolemic polycythemia in newborn dogs.

The effect of hypervolemic polycythemia (Hct 62-77) on O2 transport and O2 consumption (Vo2) was studied in 16 unanesthetized newborn dogs (age 3-10 days). A control group of 10 newborn dogs (3-10 days old) was made hypervolemic but not polycythemic in an otherwise identical experiment. Hypervolemia was attained by infusing 33 ml/kg of either packed red blood cells (polycythemia) or whole blood (controls). In the polycythemic group as a result of the transfusion, cardiac output (CO) decreased by 50% (P less than 0.001), peripheral vascular resistance (PVR) increased by 170% (P less than 0.001), but O2 transport did not change significantly, and Vo2 decreased only slightly by 13% (P less than 0.01). In the 10 control animals there were no significant changes in CO, PVR, O2 transport, or Vo2 as a result of the transfusion. Blood lactate increased only slightly in experimental (35%, P less than 0.04) and control animals (23%, NS). The ability of the animals to increase their O2 transport and Vo2 was tested by measuring the changes induced by cold stress. Cold stress produced a 20% increase in Vo2 (P less than 0.05) in both the polycythemic and the control animals. Thus in spite of a decreased CO in the nonstressed state the polycythemic animals were still able to increase O2 transport and Vo2 in response to cold stress. These results suggest that the newborn animal is capable of regulating CO to maintain O2 transport appropriate to uptake under conditions of hypervolemic, polycythemic hyperviscosity, and environmental cold stress.

Morphine increases hypothalamic noradrenaline turnover but rather decreases its enhancement induced by stress in rats.

By measuring levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), we investigated the effects of morphine on hypothalamic noradrenergic neurons in stressed or non-stressed states in male rats. Subcutaneous administration of morphine at 3 mg/kg and 6 mg/kg reduced NA level and elevated MHPG-SO4 level in the hypothalamus in a dose-dependent manner and these effects of morphine were completely abolished by pretreatment with naloxone at 0.5 mg/kg and 5 mg/kg (s.c.). Immobilization stress caused significant reduction of NA and increase in MHPG-SO4 level, and this stress-induced increase in NA turnover was attenuated by pretreatment with 3 mg/kg and 6 mg/kg of morphine. Attenuation of stress-induced enhancement of hypothalamic NA turnover by morphine was almost completely reversed by naloxone at 0.5 mg/kg and 5 mg/kg. These results suggest that morphine produces different effects on hypothalamic noradrenergic neurons, depending on the state of the animal treated, i.e., facilitation in the non-stressed state and inhibition in the stressed state and that these actions occur via opiate receptors. It is further suggested that the hypothalamic opioid peptide system might be partially involved in the stress process by attenuating increased NA turnover by stress in rats.

Cholinergic influences on hypothalamic-pituitary-adrenocortical activity of stressed rats: an approach utilizing agonists and antagonists.

Cholinergic involvement in the regulation of the hypothalamic-pituitary-adrenocortical (HPA) system of male rats was evaluated using muscarinic (atropine and methacholine) and nicotine (mecamylamine and nicotine) agents, which were selected for their specificity on cholinergic receptors (ChR). They were administered either intracerebroventricularly (icv) to produce central effects, or ip to produce both central and peripheral effects, prior to subjecting the animals to either auditory or hypercapnic stress for 1 h. Plasma corticosterone was used as an index of HPA activity. The results suggest that central muscarinic ChR are involved in inhibiting HPA activity in both non-stressed and stressed animals, whereas central nicotinic ChR are excitatory during stress but inactive in the non-stressed state. Stimulation of peripheral nicotinic ChR appeared to potentiate the HPA response to hypercapnia, and to inhibit the central excitatory nicotinic ChR when the latter were activated in non-stressed and auditory stress rats. These data suggest that during auditory stress the HPA system is more dependent upon the cholinergic system for its activation than during non-stressed and hypercapnic states.

The effects of atenolol and propranolol upon lipolysis.

1 The effects of selective and non-selective beta-adrenoceptor blockade upon plasma non-esterified fatty acid concentrations in the fasting state and following insulin stress have been studied in normal subjects. 2 Atenolol, propranolol and placebo were compared in a double-blind cross-over trial in eight normal subjects. 3 Atenolol and propranolol significantly lowered plasma non-esterified fatty acid concentrations by a similar degree in the fasting, non-stressed state. This finding suggests that beta1-adrenoceptors are involved in the control of basal lipolysis. 4 Following insulin-induced stress, lower plasma non-esterified fatty acid concentrations were observed with propranolol than with atenolol. This difference may be due to beta2-adrenoceptor involvement in the stress mechanisms controlling lipolysis, or to the differences in the water-lipid solubility properties of these drugs.

Effect of a notch on the sensitivity of high-strength steels to the environment

It was shown in [i] that, in the presence of a severe stress raiser such as a crack about 0.1 mm deep, high-strength steels in a stressed state may fracture under the action of corrosion-active environments (water, sodium chloride solution) and in media not corrosive to the steel in a nonstressed state (potassium bichromate solution, a solution of potassium bichromate and sodium carbonate). In this connection, it was suggested in [i] that the adsorption of water at the base of the crack may be the reason for the fracture of the steel in the above cases. Studies of the fracture of stressed specimens of high-strength steel SP-28 having a central, through fatigue crack in neutral sodium chloride solutions showed that fracture occurs in two stages: slow crack growth, associated with local anodic dissolution of metal at the tip of the growing crack, giving way to hydrogen embrittlement.

Effect of sublingually administered nitroglycerin on regional myocardial blood flow in patients with coronary artery disease

The effect of sublingually administered nitroglycerin on regional myocardial specific blood flow (in ml/min per 100 g tissue) was evaluated with a xenon-133 washout technique in 31 patients in a resting nonstressed state. Eight patients had normal coronary arteriograms (Group 1), 12 had coronary artery disease without collateral vessels (Group 2) and 11 had coronary artery disease with collateral vessels (Group 3). Although nitroglycerin caused a similar decrease in mean arterial blood pressure and blood pressure-heart rate product in all three groups, the decrease in regional myocardial blood flow was significantly less in Group 3 (-8+/-6% [mean+/-standard error of the mean]) than in Group 1 (-31+/-5%), P less than 0.05); an intermediary decrease occurred in Group 2 (-23+/-5%). Within Group 3, there was a mean increase in regional myocardial blood flow after nitroglycerin in the five patients whose collateral vessels were of a higher angiographic grade and arose from non-stenosed coronary arteries, whereas a reduction was observed in the six patients with none or only one of these findings (+10+/-7% versus -23+/-3%, P less than 0.001). This study suggests that even in the resting state, in some patients with coronary artery disease enhancement of regional myocardial blood flow can occur after sublingual administration of nitroglycerin and is probably mediated through well functioning collateral vessels. It is possible that the drug's effects on both the coronary and systemic circulation may relieve angina in some patients with coronary artery disease.

Memory effects in irradiated polyethylene

AbstractThe memory of irradiated polyethylene has been studied with emphasis on the magnitude of the restoration force exerted by the deformed polymer during the process of restoration to the nonstressed state and on the degree of completeness with which restoration occurs. The particular form of the memory effect studied has involved the deformation of the heated polymer followed by “locking‐in” of the memory via cooling. Subsequent heating restores the deformed specimen to the undeformed state. The memory effect has been studied under both nontransparency (NT) and transparency (T) deformation conditions. The effects of parameters such as the polymer properties (Tm, density, molecular weight), radiation dose, and deformation and restoration conditions on the degree of restoration and restoration force have been investigated. The results of this study may be summarized as follows. Restoration temperatures equal to or above the crystalline melting point (Tm) of the polymer are required in order to obtain complete restoration. The restoration temperature increases with increasing polymer crystalline melting point. The degree of restoration increases with increasing restoration temperature for NT deformed specimens. T deformed specimens do not begin to restore until the temperature approaches the Tm of the polymer. The restoring force increases with decreasing deformation temperature. NT deformation results in larger restoring forces and faster restoration relative to T deformation. The restoring force increases with increasing radiation dose for both T and NT deformations, the effect being greater for NT deformation. Radiation dose, however, above a minimum value does not affect the degree of restoration. The restoring force increases with increasing polymer initial molecular weight for T deformation.