Effects of microwaves on the adrenal cortex

Six-hundred-and-one male Long-Evans rats were used to study the effect of microwaves on adrenocortical secretion. Power density ranged from 0.1 to 55 mW/cm2 (SAR 0.02 to 11 W/kg). The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Serum corticosterone (CS) concentration was used as an index of adrenocortical function. Ten different exposure protocols were used to identify confounding factors influencing the sensitivity of adrenal cortex to microwave exposure. Increases in CS concentration were proportional to power density or colonic temperature and inversely proportional to the baseline CS. Increased CS concentration was never observed without increased colonic temperature and was not persistent 24 h after exposure. Acclimation (reduction in magnitude of response) could be noted after the tenth exposure. Facilitated heat loss attenuated the magnitude of CS increases by limiting the degree of hyperthermia. Ethanol enhanced the hyperthermic response and desensitized the adrenal response to microwave hyperthermia by increased baseline CS. Ether stimulated adrenal secretion irrespective of previous microwave exposure or adrenal stimulation induced by microwaves. Minor inhibition was also noted occasionally as decreased CS concentration at lower intensity (less than 20 mW/cm2) and decreased postexposure urinary CS excretion at 40 mW/cm2. Adrenal stimulation required minimally a 20 mW/cm2 (4 W/kg) or 0.7 degrees C increase in colonic temperature. An SAR lower than 4 W/kg may stimulate adrenal secretion by potentiating the hyperthermic effect if the ambient temperature is well above 24 degrees C.     

Factors producing elevated core temperature in spontaneously hypertensive rats

Core temperature (Tco) of the spontaneously hypertensive rat (SHR) is consistently higher by approximately 1 degree C than that of normotensive controls. To analyze factors producing the elevated Tco, mean skin temperature (Tsk), metabolic heat production (M), respiratory evaporative heat loss (Eres), effective tissue thermal conductance (K), systolic blood pressure (BP), and Tco were determined in eight male SHR and nine male normotensive Wistar-Kyoto (WKY) rats habituated to rest quietly in neck stock restraint while exposed to ambient temperatures (Ta) of 12.5, 17, 23, 28.5, 32, 34, and 35 degrees C. At all temperatures steady-state BP, Tco, and M were higher for SHR's than for WKY's. SHR's could maintain thermal balance up to Ta 32 degrees C, and WKY's up to 34 degrees C. Eres from SHR's was greater than from WKY's at Ta of 12.5, 17, and 28.5 degrees C. K of SHR's was not different from or was higher than K of WKY's, and K for both groups was 2.6 times greater at Ta 32 degrees C than at 17 degrees C. These results indicate that the high Tco of SHR's is due to increased M uncompensated by increased K or Eres.     

Abnormalities of the thyroid hormone negative feedback regulation of TSH secretion in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) are characterized by several neuroendocrine abnormalities including a chronic hypersecretion of thyrotropin (TSH) of unknown etiology. We hypothesized that the inappropriately high TSH secretion in SHR may be the result of an impaired thyroid hormone negative feedback regulation of hypothalamic thyrotropin-releasing hormone (TRH) and/or pituitary TSH production. To test this hypothesis, SHR or their normotensive Wistar-Kyoto (WKY) controls were treated with either methimazole (0.02% in drinking water) to induce hypothyroidism or administered L-thyroxine (T4) at a dose of 0.8 or 2.0 micrograms/100 g body weight/day to induce hyperthyroidism. All treatments were continued for 14 days after which animals were killed under low stress conditions. TSH concentrations in plasma and anterior pituitary tissue were 2-fold higher (P less than 0.01) in euthyroid SHR compared to WKY control rats while thyroid hormone (T3 and T4) levels were in the normal range. Hypothyroidism induced by either methimazole or thyroidectomy caused a significant (P less than 0.01) rise of plasma TSH levels in both WKY and SHR rats. However, relative to the TSH concentrations in control animals, the increase of plasma TSH in SHR was significantly blunted (P less than 0.01) in comparison to the WKY group. Hypothyroidism caused a significant depletion of TRH in stalk-median eminence (SME) tissue in both groups of rats. However, no differences between SHR and WKY rats were observed. The administration of thyroid hormone caused a dose dependent suppression of plasma TSH levels in both strains of rats. However, at both doses tested plasma TSH concentrations in SHR rats were significantly less suppressed (P less than 0.05) than those in WKY animals. Under in vitro conditions basal and potassium induced TRH release from SMEs derived from SHR was significantly (P less than 0.05) higher than that from WKY rats, whether expressed in absolute terms or as percent of content. These findings suggest that the thyroid hormone negative feedback regulation of TSH secretion may be impaired in SHR rats. Our data do not allow conclusions as to whether defects in the regulation of TSH production are located exclusively at the hypothalamic level. Since the overproduction of hypothalamic TRH and hypophysial TSH should lead to an increased thyroid hormone biosynthesis other defects in the hypothalamus-pituitary-thyroid-axis may contribute to the abnormal regulation of TSH secretion in SHR rats.     

Altered hypothalamic monoamine metabolism and pituitary prolactin regulation in female spontaneously hypertensive rats

Prolactin (PRL) secretion after aromatic amino acid decarboxylase inhibition with NSD-1015 was significantly elevated in female spontaneously hypertensive rats (SHR) as compared to normotensive (WKY) controls. Although basal PRL levels tended to be elevated in SHR rats, the differences were not significant. In vitro PRL secretion was also significantly elevated in the SHR rats as compared to the WKY rats, but the SHR rats were more responsive to the inhibitory effects of dopamine (DA). Despite changes in pituitary PRL secretion and DA response, there was no apparent difference in tubero-infundibular DA activity between the two rat strains. Hypothalamic serotonin levels were elevated in SHR rats, but metabolism did not appear to be significantly changed based on measurements of 5-hydroxytryptophan accumulation after NSD-1015 treatment.     

Hyperthermia in radiofrequency-exposed rhesus monkeys: a comparison of frequency and orientation effects

To compare the effects of exposure to a near-resonant frequency of microwaves at two orientations with a higher frequency exposure, five rhesus monkeys were exposed for 4 hr to 225 MHz, electric field oriented parallel to the long axis of the body (225 MHz-E), and to 225 MHz, magnetic field orientation (225 MHz-H), or to 1290 MHz, electric field orientation. On a separate occasion, the monkeys were exposed at night to 225 MHz-E. Exposures were conducted with the animal chair restrained in an anechoic chamber with rectal temperature continuously monitored. Blood samples were taken hourly during the 225-MHz-E exposures for cortisol analysis. The power densities used were 0, 1.2, 2.5, 5.0, 7.5, 10.0, and 15.0 mW/cm2 for 225 MHz-E (day), 0 and 5 mW/cm2 (225 MHz-E night and 225 MHz-H), and 0, 20, 28, and 38 mW/cm2 (1290 MHz). The monkeys were unable to tolerate exposure at power densities equal to or greater than 7.5 mW/cm2 (5.1 W/kg) at 225 MHz-E for longer than 90 min. The criterion for tolerance was that the rectal temperature would not exceed 41.5 degrees C. Average rectal temperature increases for day exposure to 225 MHz-E were 0.4 and 1.7 degrees C for 4-hr exposures to 2.5 and 5.0 mW/cm2 (1.7 and 3.4 W/kg). No changes in circulating cortisol levels occurred during any exposures to 5 mW/cm2 or less. Night exposures to 5 mW/cm2 (3.4 W/kg) at 225 MHz-E raised mean rectal temperature 2.1 degrees C. Exposure to 5 mW/cm2 (1.2 W/kg) at 225 MHz-H for 4 hr resulted in a 0.2 degree rise in mean rectal temperature. For 4 hr of 1290-MHz exposure to 20, 28, or 38 mW/cm2 (2.9, 4.0, and 5.4 W/kg), the mean body temperature increases were 0.4, 0.7, and 1.3 degrees C, respectively. The degree of hyperthermia caused by radiofrequency (rf) exposure was shown to be frequency and orientation dependent for equivalent power densities of exposure.     

Transport of univalent cations across the erythrocyte membrane of hypertensive rats of various ages

In the erythrocytes incubated at low temperature (3-6 degrees C), the uptake of Li+ in 6- and 16-week old spontaneously hypertensive rats (SHR) was significantly higher than in the normotensive rats (WKY) of the same age. During the incubation of cells at 37 degrees C no difference occurred in either ouabain-sensitive or ouabain-resistant fluxes of Rb+, Na+ and Li+ between the 16-week old SHR and the WKY. K+ efflux from the erythrocytes at 3 degrees C was consistently stimulated after addition to the incubation medium of 1 mmol/l Ca2+. The value of Ca2+-dependent K+-transport was significantly elevated in 16-week old SHR than in the WKY, but there was no difference in 6-week old rats. Propranolol-induced Ca2+-dependent K+ efflux from the cells at 22 degrees C was markedly higher in 6- and 16-week old SHR as compared with the WKY. The results provide a further evidence in favor of the hypothesis on the existence of a "membrane defect" in red blood cells in the SHR.     

Dynorphins and leu-enkephalin in brain nuclei and pituitary of WKY and SHR rats

The distribution of dynorphin 1–13 (Dyn-1–13, Dyn-(1–8) and Leu⁵-enkephalin (LE) immunoreactivities (ir) were determined in discrete brain nuclei of normotensive (WKY) and hypertensive (SHR) rats. The concentration of ir-Dyn-(1–13) and ir-Dyn-(1–8) varied markedly among the various nuclei studies with a predominance of ir-Dyn-(1–13) over ir-Dyn-(1–8) in all the nuclei of both WKY and SHR rats. Ir-LE also showed large variations in different sites and no consistent relationships were found between the distribution of ir-Dyn-(1–8), Dyn-(1–13) and LE. SHR rats had lower levels of ir-Dyn-(1–13), Dyn-(1–8) and LE in the suprachiasmatic nucleus compared with WKY rats. In addition, SHR rats had lower levels of ir-Dyn-(1–8)- in the paraventricular and central amygdala, and higher ir-Dyn-(1–13) levels in the substantia nigra. The level of ir-Dyn-(1–13) in the neurointermediate lobe (NIL) of SHR rats was decreased substantially compared with that of WKY rats. The localization of these opioid peptides suggests that dynorphin-like peptides may serve a variety of hypothalamic and extrahypothalamic functions which might differ between SHR and WKY rats.     

Sodium intake is increased by social stress and the Y chromosome and reduced by clonidine

The objectives were to determine 1) if female rats have higher Na intake than males and if social stress increases Na intake, 2) if the sympathetic nervous system (SNS) mediates the stress effects and the gender effect, and 3) if the Y chromosome (Yc) from a hypertensive father increases Na intake. Four rat strains (n = 10/group) of both sexes were used: 1) Wistar Kyoto normotensive (WKY), 2) an F(16) backcross with a Yc from a hypertensive father (SHR/y), 3) spontaneously hypertensive rat (SHR), and 4) an F(16) backcross with a Yc from a normotensive father (SHR/a). Females showed greater baseline Na intake than males (hypertensive strains), intruder stress increased Na intake, and clonidine decreased Na intake, but not in WKY or SHR females. SHR/y males had higher baseline Na intake compared with WKY males. In conclusion, the higher Na intake in females during baseline and stress was partially mediated through the SNS in hypertensive strains and the SHR Yc was partially responsible for the increased Na intake in SHR/y and SHR males compared with WKY.     

Comparison of SHR, WKY and Wistar rats in different behavioural animal models: effect of dopamine D1 and alpha2 agonists

Spontaneously hypertensive rats (SHR) and its counterpart, the Wistar-Kyoto rats (WKY), are probably the most often used animal model of ADHD. However, SHR as model of ADHD have also been criticised partly because of not differing to outbred rat strains. In the present study, adolescent SHR, WKY and Wistar rats from Charles River were tested in open-field, elevated plus maze and novel object recognition and on gastrointestinal transport to more intensively evaluate the strain characteristics. Non-habituated SHR and Wistar rats were more active than WKY rats but contrary to Wistar rats SHR stay hyperactive in a familiar environment. SHR were more sensitive to the alpha2-adrenoceptor agonist guanfacine and the dopamine D1 agonist A-68930 than WKY and Wistar rats, whereas amphetamine, the D1/D5 agonist ABT431 and the D2 agonist quinpirole, similarly affected open-field activity in all strains. In the elevated plus maze, SHR and Wistar rats showed less anxiety-related behaviour than WKY rats. Guanfacine and amphetamine induced an anxiolytic-like activity in SHR but not in WKY and Wistar rats. SHR showed the highest long-term memory in the novel object recognition. Gastrointestinal transport was similar and comparably affected by guanfacine in all rat strains. The present study shows clear differences in the behaviour of SHR and Wistar rats but also of WKY and Wistar rats. The use of SHR as animal model of ADHD is supported.     

Clonidine fails to reduce pressor responsiveness of conscious spontaneously hypertensive rats to vasopressin

Pressor responses and heart rate responses to intravenous injections (3.5-50.0 pmol/kg) of arginine vasopressin (AVP) were recorded in saline- and clonidine-treated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Clonidine (20 micrograms/kg, i.v.) caused a marked fall of arterial pressure in SHR but not in WKY rats so that, 20 min after the injection of the alpha 2-adrenoceptor agonist, arterial pressure was similar in the two strains of rats. The curve expressing the relationship between the dose of AVP and the increase of arterial pressure for saline-treated SHR was positioned to the left of that for saline-treated WKY rats. This enhanced pressor responsiveness of SHR to AVP may have been related to impaired reflex activity since heart rate fell much less in SHR than in WKY rats for a given elevation in pressure. Pressure responses to AVP were augmented by clonidine in both SHR and WKY rats so that, similar to saline-treated rats, pressor responsiveness to the peptide was still greater in SHR. Heart rate responses to AVP were not altered significantly by clonidine. The results indicate that clonidine fails to enhance reflex activity and reduce pressor responsiveness of SHR to AVP. The increased pressor responsiveness of both SHR and WKY rats to AVP following clonidine was an unexpected finding and may be related to a peripheral interaction between alpha-adrenergic agonists and AVP.     

Long-term left ventricular echocardiographic follow-up of SHR and WKY rats: effects of hypertension and age

Long-term follow-up of left ventricular (LV) function using echocardiography has not been reported and, in this study, was carried out in normotensive (WKY) rats and spontaneously hypertensive rats (SHR). In 10 WKY rats and SHR, LV diastolic and systolic diameter (LVEDD and LVSD), shortening fraction (SF), and weight (LVW) were determined at 8, 15, 20, 35, and 80 wk of age. The ratio of early to late mitral flow and mitral annulus velocity (VE/VA and Em/Am), isovolumic relaxation time (IVRT), deceleration time of the E wave (DTE), Tei index, and mitral flow propagation velocity (Vp) were measured. No difference in LVEDD was found between SHR and WKY rats; however, LVEDD was increased at 80 wk in both strains. SF decreased slightly in old WKY rats. LVW progressively increased from 20 to 80 wk in both strains and was greater in SHR. VE/VA and Em/Am decreased at 80 wk in WKY rats. LV relaxation (IVRT, Tei index, and Vp) was progressively impaired in SHR compared with WKY rats. LV compliance (DTE) was altered in old SHR. Echocardiography permitted a long follow-up of LV function in SHR and WKY rats. Ventricular relaxation was impaired early in the life of SHR and progressed with aging. Furthermore, LV compliance was altered, but systolic function remained unchanged, in old SHR. In contrast, relaxation and SF were only slightly altered in old WKY rats, suggesting that pressure-related changes in LV function were the dominant features in the SHR.     

Effects of angiotensin II type 1 receptor blockade on the oxidative stress in spontaneously hypertensive rat tissues

The aim of this work was to investigate the production of oxidative damage in homogenized kidney, liver and brain of spontaneously hypertensive rats (SHR), as well as the involvement of angiotensin (Ang) II in this process. Groups of 12-week-old SHR and Wistar Kyoto rats (WKY) were given 10 mg/kg/day losartan in the drinking water during 14 days. Other groups of WKY and SHR without treatment were used as controls. The production of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) were determined. No significant difference in TBARS was observed between untreated SHR or WKY rats; GSH content was lower in the liver but higher in the brain of SHR compared to WKY rats. In tissues from the SHR group, SOD and Gpx activities were reduced, whereas CAT activity was slightly increased in kidney. TBARS levels did not change in WKY rats after losartan administration, but were reduced in SHR liver and brain. Losartan treatment decreased GSH content in WKY kidney, but increased GSH in SHR liver. The activity of the antioxidant enzymes was not modified by losartan in WKY rats; however, their activities increased in tissues from treated SHR. The lower activity of antioxidant enzymes in tissues from hypertensive rats compared to those detected in normotensive controls, indicates oxidative stress production. Ang II seems to play no role in this process in normotensive animals, although AT1 receptor blockade in SHR enhances the enzymatic activity indicating that Ang II is implicated in oxidative stress generation in the hypertensive animals.     

Prenatal and early postnatal dietary sodium restriction sensitizes the adult rat to amphetamines

Acute sodium deficiency sensitizes adult rats to psychomotor effects of amphetamine. This study determined whether prenatal and early life manipulation of dietary sodium sensitized adult offspring to psychomotor effects of amphetamine (1 or 3 mg/kg ip) in two strains of rats. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) dams were fed chow containing low NaCl (0.12%; LN), normal NaCl (1%; NN), or high NaCl (4%; HN) throughout breeding, gestation, and lactation. Male offspring were maintained on the test diet for an additional 3 wk postweaning and then fed standard chow thereafter until testing began. Overall, blood pressure (BP), total fluid intake, salt preference, and adrenal gland weight were greater in SHR than in WKY. WKY LN offspring had greater water intake and adrenal gland weight than did WKY NN and HN offspring, whereas WKY HN offspring had increased BP, salt intake, and salt preference compared with other WKY offspring. SHR HN offspring also had increased BP compared with other SHR offspring; all other measures were similar for SHR offspring. The low-dose amphetamine increased locomotor and stereotypical behavior compared with baseline and saline injection in both WKY and SHR offspring. Dietary sodium history affected the rats' psychomotor response to the higher dose of amphetamine. Injections of 3 mg/kg amphetamine in both strains produced significantly more behavioral activity in the LN offspring than in NN and HN offspring. These results show that early life experience with low-sodium diets produce long-term changes in adult rats' behavioral responses to amphetamine.     

The relationship of decreased serum thyrotropin and increased colonic temperature in rats exposed to microwaves

Although decreased serum thyrotropin (TSH) concentration has been found to be part of the endocrine response pattern in rats exposed to microwaves and other stimuli, the response of individual endocrine organs was not activated simultaneously by a given irradiance. Therefore, analytical evaluation of the function of endocrine organs individually as well as collectively is required to characterize the extent of biological involvement in microwave exposure. We have studied the changes in TSH concentration in unanesthetized rats exposed to 2.45 GHz amplitude modulated (120 Hz) microwaves in the far field for 2 and 4 h, between 0 and 55 mW/cm2, and from 1 to 10 times to demonstrate any possible cumulation, acclimation, or sensitization process. Ether inhalation was administered to test the responsiveness of TSH in groups of rats that failed to respond to microwave exposure by lowering TSH concentration. In addition, groups of rats were sampled 24 h after microwave exposure to test the persistency of the microwave effect on serum TSH concentration. Results showed that TSH concentration decreased in rats after microwave exposure. Influence of microwave exposure on serum TSH concentration was independent of the number of exposures indicating absence of cumulation, acclimation, or sensitization. The microwave effect on serum TSH could be dependent on duration of exposure. Decreased TSH concentration was usually accompanied by increased colonic temperature. For 4-h exposure, the lowest irradiance was 20 mW/cm2 or a 0.3 degree C increase in colonic temperature independent of the number of exposures. For 2-h exposure, the lowest irradiance was 30 mW/cm2 or a 1.1 degree C increase in colonic temperature regardless of the number of exposures. All the rats exposed at 10 mW/cm2 for 2 h had a lower TSH concentration than those of sham-exposed rats. Occasionally, significant reduction in TSH concentration could not be found in rats exposed to 20 or 25 mW/cm2 for 2 h. None of the rats exposed at an irradiance lower than 10 mW/cm2 had any change in TSH concentration. Failure of change in TSH concentration in response to microwave exposure was not a reflection of a deficiency since these rats responded to ether inhalation by lowering their TSH concentration. The effect of microwave exposure on TSH concentration was not persistent after exposure. The relation between TSH concentration and colonic temperature was curvilinear (exponential). From these results, two mechanisms and their implications for man were discussed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Acute haemodynamic effects and tissue distribution of acebutolol in normotensive and spontaneously hypertensive rats

Acute i.v. administration of 15 mg/kg acebutolol in normotensive (WKY), Okamoto (SHR) and Okamoto stroke-prone (SHR-SP) awake rats resulted in weak effects on blood pressure and in bradycardia more marked in SHR-SP. Thirty minutes after i.v. administration, lung and renal uptake of [14C]acebutolol was reduced in SHR compared to other rats. Muscle uptake was higher in SHR and blood concentration was higher in SHR-SP. Brain levels were low and similar in all rats. Plasma protein binding was identical in all rats. These results are discussed according to the characteristics of the three strains studied.     

Cold-restraint induced gastric lesions in normotensive and spontaneously hypertensive rats

Spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats were subjected to 2 hr of cold-restraint stress at 2–6°C following a 24 hr fast. WKY rats had a significantly greater incidence and degree of ulceration of the gastric glandular mucosa than did SHR rats. Mean arterial pressure, obtained from a chronic arterial cannula, fell during 2 hr of cold-restraint stress in both SHR and WKY rats. Heart rate was unchanged in WKY but fell significantly in SHR. Plasma norepinephrine (NE) and epinephrine (E), determined by radioenzymatic assay, increased significantly following stress. Increased levels of NE remained similar for both SHR and WKY rats, while post-stress levels of E for the SHR rats greatly exceeded E levels for WKY rats. A greater degree of hypothermia was also noted in SHR rats. Decreased stress induced ulcerogenesis in the SHR may be due to the well-known altered hemodynamic and autonomic nervous system reactivity in this strain or other factors not yet discovered.     

Cardiovascular changes in unanesthetized and ketamine-anesthetized Sprague-Dawley rats exposed to 2.8-GHz radiofrequency radiation.

Sprague-Dawley rats were exposed to 2.8-GHz radiofrequency radiation, first while unanesthetized and then while anesthetized with ketamine (150 mg/kg.I.M.). Irradiation at a power density of 60 mW/cm2 (whole-body average specific absorption rate of approximately 14 W/kg) was conducted for sufficient duration to increase colonic temperature from 38.5 to 39.5 degrees C. The time required for the temperature increase was significantly longer in the anesthetized state. During irradiation, heart rate increased significantly both with and without anesthesia, while mean arterial blood pressure increased only when the rats were unanesthetized. The heart rate increase in the anesthetized state contrasts with a lack of change in a previous study of Fischer rats. This difference between anesthetized Sprague-Dawley and Fischer rats should be considered when comparing cardiovascular data obtained from these two strains of rats.     

Secretory dysfunction of vascular endothelium limits the effect of angiotensin converting enzyme inhibitor quinapril on aggregation of erythrocytes in experimental hypertension.

Using automatic erythrocyte aggregometer type MA-1 (Myrenne gmbh, Germany), we investigated the hypothesis that therapeutic effectiveness of quinapril--angiotensin converting enzyme inhibitor (ACEI)--in the treatment of hypertension would correlate with improvement of red blood cell (RBC) aggregability. Experiments were performed on commercially available inbred strain of spontaneously hypertensive male rats (SHR) aged 19-21 weeks. Age-matched normotensive Wistar-Kyoto (WKY) rats genetically related to SHR were used as a control. Aggregability of RBC in hypertensive rats was significantly higher than in control WKY animals. Quinapril (100 microg/kg) administered i.p. for 8 days improved RBC aggregability in normotensive rats but surprisingly not in SHR animals. Beneficial effect of quinapril on RBC aggregation observed in normotensive animals did not occur when this drug was injected in combination with aspirin (1 or 50 mg/kg) or with indomethacin (20 mg/kg) or with L-NAME (10 mg/kg). However, much the same damaging effects on RBC aggregability were observed when aspirin, indomethacin or L-NAME were each administered into normotensive animals without quinapril. In contrast with normotensive rats, aggregability of RBC in SHR was not affected either by quinapril or by indomethacin and by L-NAME, given separately or in combination. The only compound significantly worsening RBC aggregability in SHR was aspirin but this effect was not dose-dependent. Quinapril-induced improvement of RBC aggregability in normotensive rats (but not in SHR) was completely abolished by simultaneous administration of B2 receptor antagonist icatibant and successfully mimicked by 8 days of treatment with bradykinin. In vitro aggregability of RBC isolated from WKY was not affected by previous incubation (30 min at 37 degrees C) with quinapril, indomethacin or L-NAME. Only aspirin (3 mM) significantly increased RBC aggregability as compared to placebo. It is concluded that under physiological conditions quinapril efficiently inhibits RBC aggregability and this effect is modulated by secretion of endothelial mediators, mainly prostacyclin and nitric oxide. In hypertension quinapril, in spite of lowering of arterial blood pressure, is unable to display its beneficial effects on RBC aggregability possibly due to the hypertension-induced/accompanied dysfunction of vascular endothelium. Aspirin revealed unique erythrocyte damaging properties, presumably independent of inhibition of cyclooxygenase but related to a direct membrane protein acetylation.     

Endorphinergic mechanism in the central cardiovascular and analgesic effects of clonidine

In urethane-anesthetized male rats, injection of 5 nmol clonidine into the nucleus of the solitary tract (NTS) causes hypotension and bradycardia. These effects are greater in spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley (SD) rats than in normotensive Wistar-Kyoto (WKY) rats. The effects of clonidine are stereoselectively inhibited by 100 ng intra-NTS naloxone in SHR and SD but not in WKY rats. In SHR, the effects of clonidine are also inhibited by intra-NTS administration of ICI 174864 (a delta-receptor antagonist) but not by beta-funaltrexamine (a mu-receptor antagonist), while in SD rats only the mu- and not the delta-antagonist was effective. Neonatal treatment of SHR with monosodium glutamate (MSG) reduced the beta-endorphin content of the arcuate nucleus and the NTS, reduced the cardiovascular effects of clonidine, and abolished their naloxone sensitivity. MSG treatment of newborn WKY reduced the beta-endorphin content of the arcuate nucleus but not the NTS and did not affect the responses to clonidine. Measurement of pain sensitivity by the formalin test indicated that clonidine was more potent as an analgesic in SHR and SD than in WKY rats, and its effect was inhibited by naloxone (2 mg/kg i.p.) in the former two strains but not in WKY. It is proposed that a naloxone-sensitive component of the cardiovascular effects of clonidine is due to release of a beta-endorphin-like opioid from the NTS, and that this mechanism is present in SHR and SD but not in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of ambient temperatures ranging from cold to heat on thermoregulation in conscious MK801-treated rats

The glutamate NMDA receptor has been suggested to be involved in thermoregulation. To further analyse its role, the thermoregulatory responses of rats treated with 0.5 mg.kg-1 of dizocilpine (MK801) were compared with those of control rats treated only with the same volume of saline during a 180-min exposure at one of the six different ambient temperatures, ranging from cold to heat. Colonic temperature (Tco) and tail skin temperature (Ttail) were measured throughout using Cu-Ct thermocouples. In the cold (2.4 and 12.3 degrees C), Tco decreased either sharply (MK801) or progressively (saline), reaching the same final value (2.4 degrees C) or a lower value in the MK801-treated rats (12.3 degrees C). At the same time, Ttail decreased in both groups. In the cool environment (20.7 degrees C), Tco and Ttail decreased in both groups, with lower final values in MK801-treated rats. At thermoneutrality (28.8 degrees C), the MK801-induced hyperthermia remained steady, while Ttail increased in both groups. In the heat (34.6 and 36.2 degrees C), Tco and Ttail increased in both groups, with higher final values in MK801-treated rats. Moreover, at 36.2 degrees C, only MK801-treated rats exhibited heatstroke. It is thus suggested that MK801-induced inhibition of NMDA receptors impairs thermoregulation, especially in the heat.