Hypoxic initiation of pulmonary hypertension is mediated by serotonin secretion from neuroepithelial bodies in chemodenervated dogs

The purpose of this study was to investigate the stimulatory effect of hypoxia on the secretion of serotonin by neuroepithelial bodies (NEB) as well as to determine the relation between its level and changes in pulmonary arterial pressure (PAP) and also to determinate the effect of serotonin antagonists (pizotifen and methysergide) on the responses of pulmonary and systemic arterial pressures. The experiments were carried out in peripheral chemoreceptor-denervated dogs anesthetized with Na penthabarbital (30 mg/kg i.v.). On the breathing of normoxic and hypoxic (7% O2-93% N2) gas mixtures and on the injection of KCN (80 microg/kg i.v.), PAP, systemic arterial blood pressure (BP), tidal volume (VT), respiratory frequency (f/min), ventilation minute volume (VE) were determined. Also PAP and BP were recorded before and after the injection of pizotifen (0.5 mg/kg i.v.) and methysergide (1 mg/kg i.v.) during normoxic or hypoxic gas mixture breathing. At the end of each experimantal phase, serotonin level, PaO2, PaCO2 and pHa values in blood samples obtained from left ventricle and femoral artery were determined. On the breathing of the hypoxic gas mixture of the chemodenervated dogs, VT, VE and BP significantly decreased (P < 0.001, P < 0.001, P < 0.01). The mean value of PAP and serotonin levels (ventricular and femoral) were found significantly increased when compared with the corresponding normoxic values (P < 0.001, P < 0.05). On the other hand, injection of KCN produced no significant changes in PAP, serotonin levels, BP and respiratory parameters. After the injection of pizotifen, PAP was significantly increased in hypoxia (P < 0.01). After the injection of methysergide, the response of PAP was completely abolished during the breathing of hypoxic gas mixture. The finding of the abolition of response of PAP to hypoxia after the injection of methysergide indicates that serotonin release from NEB may be responsible for the elevation of PAP in hypoxic hypoxia.     

Effects of pituitary adenylate cyclase-activating polypeptide on cardiovascular and respiratory responses in anaesthetised dogs

This study examines some of the cardiovascular and respiratory effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in anaesthetised dogs. Intravenous injection of PACAP 27 caused an increase in arterial blood pressure and an increase in heart rate. The blood pressure response was significantly reduced by adrenoceptor blockade suggesting a mechanism of action mediated in part via catecholamines. The heart rate increase was unaltered by adrenoceptor blockade suggesting a direct effect of PACAP 27. PACAP 27 also caused potentiation of cardiac slowing caused by stimulation of the vagus nerve. In addition, PACAP 27 powerfully stimulated breathing. This was probably evoked by stimulation of arterial chemoreceptors, because bilateral section of the carotid sinus nerves abolished this effect. PACAP 27 had no effect on the ability of the cardiac sympathetic nerve to increase heart rate, nor on the interaction between the sympathetic and parasympathetic systems in the heart.     

Distribution of respiratory muscle and organ blood flow during endotoxic shock in dogs

Respiratory muscle blood flow and organ blood flow during endotoxic shock were studied in spontaneously breathing dogs (SB, n = 6) and mechanically ventilated dogs (MV, n = 5) with radiolabeled microspheres. Shock was produced by a 5-min intravenous injection of Escherichia coli endotoxin (0.55:B5, Difco, 10 mg/kg) suspended in saline. Mean arterial blood pressure and cardiac output in the SB group dropped to 59 and 45% of control values, respectively. There was a similar reduction in arterial blood pressure and cardiac output in the MV group. Total respiratory muscle blood flow in the SB group increased significantly from the control value of 51 +/- 4 ml/min (mean +/- SE) to 101 +/- 22 ml/min at 60 min of shock. In the MV group, respiratory muscle perfusion fell from control values of 43 +/- 12 ml/min to 25 +/- 3 ml/min at 60 min of shock. In the SB group, 8.8% of the cardiac output was received by the respiratory muscle during shock in comparison with 1.9% in the MV group. In both groups of dogs, blood flow to most organs was compromised during shock; however, blood flow to the brain, gut, and skeletal muscles was higher in the MV group than in the SB group. Thus by mechanical ventilation a fraction of the cardiac output used by the working respiratory muscles can be made available for perfusion of other organs during endotoxic shock.     

Reversal of endotoxin-mediated shock by NG-methyl-L-arginine, an inhibitor of nitric oxide synthesis

Septic shock is a life-threatening condition that results from exposure to bacterial endotoxin. It is manifested by cardiovascular collapse and mediated by the release of cytokines such as tumor necrosis factor. Some of these cytokines cause the release of vasoactive substances. In the present study, administration of 40 microgram/kg of bacterial endotoxin to dogs caused a 33% decrease in peripheral vascular resistance and a 54% fall in mean arterial blood pressure within 30 to 90 minutes. Vascular resistance and systemic arterial pressure returned to normal within 1.5 minutes after intravenous administration of NG-methyl-L-arginine (20 mg/kg), a potent and selective inhibitor of nitric oxide synthesis. L-Arginine reversed the effect of L-NMA and restored the endotoxin-induced hypotension. Although NG-methyl-L-arginine injection increased blood pressure in control dogs, the hypertensive effect was much greater in endotoxemic dogs (24.8 +/- 2.7 mmHg vs 47.8 +/- 6.8 mmHg, p = 0.01, n = 4). NG-Methyl-L-arginine caused only a modest increase in blood pressure in dogs made hypotensive by continuous intravenous infusion of nitroglycerin (17.1 +/- 5.0 mm Hg, n = 3). These findings suggest that nitric oxide overproduction is an important contributor to endotoxic shock. Moreover, our findings demonstrate for the first time, the utility of nitric oxide synthesis inhibitors in endotoxic shock and suggest that such inhibitors may be of therapeutic value in the treatment of septic shock.     

Circulatory effects of prolonged hypoxia before and during antihistamine.

Five chronically instrumented healthy dogs were exposed to a 5-day period of breathing 10% oxygen in a chamber. The response to hypoxia was found to be time dependent. During the first 24 h of hypoxia the circulatory response was characterized by increases in cardiac output, heart rate, pulmonary and systemic arterial blood pressures, and pulmonary vascular resistance. Systemic vascular resistance increased; left atrial pressure decreased. During the early part of hypoxia the animals became hypocapnic; the arterial blood pH rose significantly. During the rest of the hypoxic period cardiac output, heart rate, and arterial blood pH returned to the control values; pulmonary and systemic arterial pressures and pulmonary vascular resistance remained significantly elevated. Systemic vascular resistance rose; left atrial pressure remained below control. This response to hypoxia was not substantially modified when the experiment was repeated during the administration of the antihistamine promethazine, an H1-receptor blocking agent, in a dose which blocked the pulmonary vasoconstrictor response to small doses of exogenous histamine. The circulatory response to acute hypoxia in five anesthetized dogs was not modified by intravenous administration of metiamide, an H2-receptor blocking agent.     

Echinococcus granulosus: Permeability of hydatid cysts to mebendazole in mice

Mice infected with Echinococcus granulosus were given one dose of 15 mg kg^?1 of ¹⁴C-mebendazole by gavage. Blood, hydatid cyst fluid and membranes were collected and counted at varying intervals thereafter. Radioactivity in blood peaked by 16 h and declined rapidly thereafter. Activity in hydatid cyst fluid paralleled that in blood but in amounts of only 5–10%. While levels of radioactivity in hydatid cyst membranes for the most part paralleled those of blood, in several samples they remained stable or increased from 16 to 48 h while those in blood had decreased to baseline. Protoscolices lost all signs of viability by 48 h after treatment.     

Echinococcus granulosus: host lymphocyte transformation by parasite antigens.

Lymphocyte transformation, measured by in vitro tritiated thymidine incorporation, and indirect hemagglutination tests were carried out on hydatid patients and normal individuals using sheep and human hydatid fluid or scolex antigens. The hydatid patients showed statistically significant lymphocyte transformation with human and sheep hydatid fluid or scolex antigens when compared to normal individuals. The indirect hemagglutination tests resulted in high titers of antibody with sheep or human hydatid fluid antigens, while very low titers were obtained with scolex antigens. Unlike in the indirect hemagglutination test, the source of the antigen, scolex or fluid, was not of consequence in the lymphocyte transformation test. Furthermore, there was no correlation between the results of the serologic and lymphocyte transformation tests, since some patients with very high lymphocyte stimulation indices produced low indirect hemagglutination titers and vice versa. Similar results were obtained from rabbits which were immunized with sheep hydatid fluid or scolex extracts. The skin tests were of the immediate type of hypersensitivity reactions. Delayed skin reactions did not occur in spite of the presence of sensitized lymphocytes in the blood of the immunized rabbits.     

Serodiagnosis of Echinococcosis by ELISA Using Cystic Fluid from Uzbekistan Sheep

According to increase of travel, the cases of imported echinococcosis have been increasing in Korea. The present study was undertaken to develop a serodiagnostic system for echinococcosis in Korea. For diagnosis of echinococcosis, the fluid of Echinococcus granulosus hydatid cysts was collected from naturally infected sheep in Uzbekistan. Also serum samples of infected patients who were surgically confirmed were collected in a hospital in Tashkent, Uzbekistan. According to the absorbance of 59 echinococcosis positive and 39 negative control serum samples, the cut-off value was determined as 0.27. The sensitivity and specificity of ELISA with hydatid fluid antigen were 91.5% and 96%, respectively. The antigen cross-reacted with the serum of some cysticercosis or clonorchiasis patients. However, immunoblot analysis on the cystic fluid recognized antigenic proteins of 7-, 16-, and 24-kDa bands in their dominant protein quantity and strong blotting reactivity. In conclusion, the present ELISA system using hydatid cyst fluid antigen from Uzbekistan sheep is sensitive and specific for diagnosis of echinococcosis cases.     

Nicotine-induced respiratory effects of cigarette smoke in dogs

We report that nicotine is responsible for both a blood-borne stimulation of the respiratory center and a direct effect on intrathoracic airway tone in dogs. We introduced cigarette smoke into the lungs of donor dogs and injected arterial blood obtained from them into the circulation of recipient dogs to show that a blood-borne material increased breathing and airway smooth muscle tone. Smoke from cigarettes containing 2.64 mg of nicotine was effective; that from cigarettes containing 0.42 mg of nicotine was not. Nicotine, in doses comparable to the amounts absorbed from smoke, also increased breathing and tracheal smooth muscle tension when injected into the vertebral circulation of recipient dogs. Finally, blockade of nicotine receptors in the central nervous system and in the airway parasympathetic ganglia inhibited the effects of inhaled cigarette smoke and intravenous nicotine on the respiratory center and on bronchomotor tone. We conclude that nicotine absorbed from cigarette smoke is the main cause of cigarette smoke-induced bronchoconstriction. It caused central respiratory stimulation, resulting in increased breathing and airway smooth muscle tension, and had a direct effect on airway parasympathetic ganglia as well.     

Inhibitory effects of CO2 on airway defensive reflexes in enflurane-anesthetized humans

We investigated responses of respiration, blood pressure, and heart rate to tracheal mucosa irritation induced by injection of distilled water at three different levels of CO2 ventilatory drive in 11 spontaneously breathing female patients under a constant depth of enflurane anesthesia [1.1 minimum alveolar concentration (MAC)]. The airway irritation at the resting level of spontaneous breathing caused a variety of respiratory responses such as coughing, expiration reflex, apnea, and spasmodic panting, with considerable increases in blood pressure and heart rate. Although the latency of respiratory responses after water injection was much shorter than those of blood pressure and heart rate responses, blood pressure and heart rate responses, once elicited, were prolonged much longer than was the respiratory response. An increase in CO2 ventilatory drive decreased the degree and duration of respiratory, blood pressure, and heart rate responses to the airway irritation, whereas a decrease in CO2 ventilatory drive had the opposite effect on these responses. Our results indicate that changes in CO2 ventilatory drive can modify reflex responses of respiration, blood pressure, and heart rate to airway irritation.     

Developmental changes in respiratory, febrile, and cardiovascular responses to PGE(2) in newborn lambs

PGE(2) has centrally mediated respiratory, febrile, and cardiovascular effects that markedly differ between fetal and adult life. We hypothesized that the transition from fetal to adult responses to PGE(2) occurs in the newborn period. Thus effects of an intracarotid infusion of PGE(2) (3 microg/min for 60 min) were determined in unanesthetized newborn lambs at 5, 10, and 15 days after birth. At 5 days, PGE(2) reduced central CO(2) sensitivity, reduced lung ventilation due to a decrease in breathing frequency, and induced hypercapnia. By 15 days, these effects of PGE(2) had waned significantly. In contrast, phasic (expiratory) thyroarytenoid muscle electromyogram activity, number of short apneas, and incidence of Biot periodic breathing were similarly increased at all three ages. PGE(2) induced a sustained fever at 10 and 15 days. Heart rate and mean arterial blood pressure were unchanged in contrast to marked increases observed by others in adults. Results showed that the transition from fetal to adult respiratory and febrile responses to PGE(2) occurs in early postnatal life, whereas adult cardiovascular responses develop later in life in sheep.     

The effects of endothelin-1 on the cardiorespiratory physiology of the freshwater trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias).

The aim of the present study was to evaluate the effects of endothelin-l-elicited cardiovascular events on respiratory gas transfer in the freshwater rainbow trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). In both species, endothelin-1 (666 pmol kg(-1)) caused a rapid (within 4 min) reduction (ca. 30-50 mmHg) in arterial blood partial pressure of O2. The effects of endothelin-1 on arterial blood partial pressure of CO2 were not synchronised with the changes in O2 partial pressure and the responses were markedly different in trout and dogfish. In trout, arterial CO2 partial pressure was increased transiently by approximately 1.0 mmHg but the onset of the response was delayed and occurred 12 min after endothelin-1 injection. In contrast, CO2 partial pressure remained more-or-less constant in dogfish after injection of endothelin-1 and was increased only slightly (approximately 0.1 mmHg) after 60 min. Pre-treatment of trout with bovine carbonic anhydrase (5 mg ml(-1)) eliminated the increase in CO2 partial pressure that was normally observed after endothelin-1 injection. In both species, endothelin-1 injection caused a decrease in arterial blood pH that mirrored the changes in CO2 partial pressure. Endothelin-1 injection was associated with transient (trout) or persistent (dogfish) hyperventilation as indicated by pronounced increases in breathing frequency and amplitude. In trout, arterial blood pressure remained constant or was decreased slightly and was accompanied by a transient increase in systemic resistance, and a temporary reduction in cardiac output. The decrease in cardiac output was caused solely by a reduction in cardiac frequency; cardiac stroke volume was unaffected. In dogfish, arterial blood pressure was lowered by approximately 10 mmHg at 6-10 min after endothelin-1 injection but then was rapidly restored to pre-injection levels. The decrease in arterial blood pressure reflected an increase in branchial vascular resistance (as determined using in situ perfused gill preparations) that was accompanied by simultaneous decreases in systemic resistance and cardiac output. Cardiac frequency and stroke volume were reduced by endothelin-1 injection and thus both variables contributed to the changes in cardiac output. We conclude that the net consequences of endothelin-1 on arterial blood gases result from the opposing effects of reduced gill functional surface area (caused by vasoconstriction) and an increase in blood residence time within the gill (caused by decreased cardiac output.     

Tolerance to low-dose endotoxin in awake sheep

Dose response and tolerance to a small intravenous dose of Serratia marcescens lipopolysaccharide (LPS) were studied in awake sheep. Core temperature significantly increased after a dose of 0.002 micrograms/kg; changes in pulmonary arterial pressure, pulmonary vascular resistance, plasma thromboxane B2, and circulating leukocyte concentration occurred after 0.02 micrograms/kg; plasma 6-keto-prostaglandin F1 alpha increased after 0.2 micrograms/kg. Development of acute tolerance was studied by injection of S. marcescens LPS (0.02 micrograms/kg iv) on 3 consecutive days: pulmonary arterial pressure and thromboxane B2 levels were significantly lower than controls after the second dose, whereas fever and the degree of leukopenia were not diminished until the third dose. After intravenous administration of LPS given in increasing doses from 0.1 to 3.2 micrograms/kg three times weekly over 7 wk, there were no measurable changes in any of the above parameters after challenge with S. marcescens LPS (0.02 micrograms/kg) after a 1-wk rest period. In awake sheep, small intravenous doses of LPS can cause physiologically important changes of the pulmonary circulation and can alter the hemodynamic and eicosanoid mediator responses to subsequent challenges with LPS. Large intravenous doses of LPS can ablate the physiological responses to subsequent small doses of LPS.     

Cardiovascular activities of intravenous methionine-enkephalin-Arg6-Phe7 and methionine-enkephalin-Arg6-Gly7-Leu8 in the conscious dog

The preproenkephalin A molecule from the adrenal medulla contains the opioid peptides methionine-enkephalin (Met-ENK), leucine-enkephalin (Leu-ENK), methionine-enkephalin-Arg6-Phe7 (heptapeptide), and methionine-enkephalin-Arg6-Gly7-Leu8 (octapeptide). In the conscious, chronically instrumented dog, Met-ENK and Leu-ENK simultaneously increase heart rate and systemic arterial pressure following intravenous administration. In 19 of 23 dogs, heptapeptide produced a response identical to Met-ENK and Leu-ENK, which was inhibited by naloxone but unaffected by the dipeptidyl carboxypeptidase inhibitor SQ20881. However, in four dogs, heptapeptide produced only a fall in systemic pressure associated with an increase in heart rate despite characteristic Met-ENK responses in the same dogs; naloxone did not appear to alter this hypotensive response. Octapeptide produced slight increases in systemic pressure and heart rate. These data suggest that heptapeptide may possess intrinsic cardiovascular activity at opiate receptors; however, in certain dogs, non-opiate mechanisms, perhaps histamine release, may predominate.     

Echinococcus granulosus: Diagnosis of human hydatid disease by the indirect haemoagglutination reaction with antigens from hydatid fluid and scoleces

Tassi Carmelo, Dottorini Silvio, Scalise Giorgio and Geranio Nadia. 1981. Echinococcus granulosus: diagnosis of human hydatid disease by the Indirect Haemoagglutination reaction with antigens from hydatid fluid and scoleces. International Journal for Parasitology11: 85–88. Various antigenic fractions were prepared from sheep hydatid fluid and scoleces of Echinococcus granulosus by ammonium sulphate salting out. Sheep red blood cells were sensitized with all antigenic preparations and tested, by Indirect Haemoagglutination reaction, against 63 sera from humans with hydatid disease and 163 controls. The greatest sensitivity was obtained with the ‘0·8 M fraction’ and ‘Band 7’ from hydatid fluid. The specificity was excellent for all antigens examined.     

Epidemiological and histomorphic studies in sheep infected with hydatid cyst in Taif area

Hydatidosis is a zoonotic disease caused by Echinococcus granulosus larvae, which affects sheep worldwide, especially in rural communities. This study aims to determine the prevalence and structure of hydatid cyst in sheep. A total number of 1,198 sheep in different age groups G1 (<1 year), G2 (1–2 years) and G3 (>2 years) were slaughtered at Taif abattoirs, then examined for the presence of hydatid cysts in lung, liver, and mesentery. Prevalence of hydatid cyst infection in imported sheep (13.0%) was higher than of local sheep (10.2%). Particularly, as per gender, prevalence of imported females (71.9%) was higher than those of local females (28.1%), while that of imported males (66.3%) was higher than those of local males (33.7%). Large sizes of hydatid cysts and fertility recorded in G3 were higher in both local and imported sheep than those of G1 and G2. Morphometric analysis of pathological lesions in liver of all infected sheep showed a significant increase compared to non-infected healthy sheep (have no lesions) (P < 0.001). In addition, for all infected sheep, histochemical investigation with Masson’s trichrome stain showed collagen fibers inside the hydatid cyst capsules and in pericystic region. The collagen fibers content and the cellular laminated membranes took the green color, while immunohistochemical evaluation detected a positive reaction for CD3.     

The effects of endothelin-1 on the cardiorespiratory physiology of the freshwater trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias)

The aim of the present study was to evaluate the effects of endothelin-1-elicited cardiovascular events on respiratory gas transfer in the freshwater rainbow trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). In both species, endothelin-1 (666 pmol kg^-1) caused a rapid (within 4 min) reduction (ca. 30-50 mmHg) in arterial blood partial pressure of O₂. The effects of endothelin-1 on arterial blood partial pressure of CO₂ were not synchronised with the changes in O₂ partial pressure and the responses were markedly different in trout and dogfish. In trout, arterial CO₂ partial pressure was increased transiently by ~1.0 mmHg but the onset of the response was delayed and occurred 12 min after endothelin-1 injection. In contrast, CO₂ partial pressure remained more-or-less constant in dogfish after injection of endothelin-1 and was increased only slightly (~0.1 mmHg) after 60 min. Pre-treatment of trout with bovine carbonic anhydrase (5 mg ml^-1) eliminated the increase in CO₂ partial pressure that was normally observed after endothelin-1 injection. In both species, endothelin-1 injection caused a decrease in arterial blood pH that mirrored the changes in CO₂ partial pressure. Endothelin-1 injection was associated with transient (trout) or persistent (dogfish) hyperventilation as indicated by pronounced increases in breathing frequency and amplitude. In trout, arterial blood pressure remained constant or was decreased slightly and was accompanied by a transient increase in systemic resistance, and a temporary reduction in cardiac output. The decrease in cardiac output was caused solely by a reduction in cardiac frequency; cardiac stroke volume was unaffected. In dogfish, arterial blood pressure was lowered by ~10 mmHg at 6-10 min after endothelin-1 injection but then was rapidly restored to pre-injection levels. The decrease in arterial blood pressure reflected an increase in branchial vascular resistance (as determined using in situ perfused gill preparations) that was accompanied by simultaneous decreases in systemic resistance and cardiac output. Cardiac frequency and stroke volume were reduced by endothelin-1 injection and thus both variables contributed to the changes in cardiac output. We conclude that the net consequences of endothelin-1 on arterial blood gases result from the opposing effects of reduced gill functional surface area (caused by vasoconstriction) and an increase in blood residence time within the gill (caused by decreased cardiac output.     

Cardiovascular and respiratory responses to slow ramp carotid sinus pressures in the dog

The respiratory and mean arterial pressure (MAP) responses to slow ramp pressure stimulation of carotid baroreceptors were compared in pentobarbital-anesthetized vagotomized dogs breathing 100% O2. Carotid sinus pressure (CSP) was raised from 50 (control) to 220 mmHg and then returned to control as linear ramps (+/- 1 mmHg/s) in isolated sinuses. MAP, heart rate (HR), ventilation (VE), frequency (f), and tidal volume (VT) were expressed as percent of control. The maximum difference between responses to positive and negative ramps at a given CSP (MAX) and the average difference (AVG) served as indicators of the hysteresis for each response. In 27 dogs MAP changed monotonically with varying CSP with insignificant (P = 0.27, MAX) or barely significant (P = 0.03, AVG) hysteresis, monotonic function being one that is continuously nondecreasing or continuously nonincreasing. Similar responses were obtained for HR. VE decreased as CSP increased, but the change was not monotonic. During negative ramp, VE increased back to control with an overshoot. Hysteresis for VE was pronounced (P less than 0.0001, both measures). The VE response was primarily determined by f; VT increased with CSP. To eliminate secondary respiratory effects due to alterations in MAP, in seven dogs similar experiments were performed after ganglionic blockade with hexamethonium. Hysteresis in VE and f persisted. To assess the role of changing arterial PCO2 (PaCO2) on VE, the CSP was held constant (after a ramp rise) at 140, 150, or 180 mmHg before reducing it at -1 mmHg/s to 50 mmHg; however, a significant hysteresis in VE was still observed. Further experiments, to eliminate secondary reflexes due to altered PaCO2, were performed in seven dogs after ganglionic blockade and paralysis with Flaxedil, with phrenic nerve activity as an indicator of ("neural") respiration. The hysteresis in VE and f were no longer significant. In summary, the results indicate that 1) slow ramp carotid baroreceptor stimulation elicits both VE and cardiovascular responses, the VE response showing a dramatically higher hysteresis than the cardiovascular responses; 2) the ventilatory hysteresis is partially explained by the secondary changes in PaCO2 and perhaps by cardiovascular variables; and 3) the central processing of the baroventilatory reflex appears to be rate sensitive at a slower rate of pressure change than that which causes rate sensitivity in the baropressure reflex.     

Cardiorespiratory responses to intracerebroventricular injection of neuropeptide Y in anaesthetised dogs.

Cardiovascular and respiratory effects of intracerebroventricular (icv) administration of neuropeptide Y (NPY) and separate, preferential agonists for NPY Y1 and Y2 receptors were observed in anaesthetised dogs. Central injections of NPY resulted in significant cardiac slowing and decreases in arterial pressure. These cardiovascular effects were blocked by central injection of the NPY Y1- preferring antagonist 1229U91. Central injection of NPY did not have a significant effect on ventilation, but the NPY Y1 antagonist 1229U91 administered alone caused a significant increase in ventilation. The NPY Y1-receptor agonist [Leu31Pro34] NPY significantly decreased ventilation while the NPY Y2 receptor agonist N-acetyl [Leu28Leu31] NPY 24--36 significantly increased it. A similar inverse relationship was seen with respect to blood pressure, with the NPY Y1-receptor agonist [Leu31Pro34] NPY significantly decreasing blood pressure, while the NPY Y2 receptor agonist N-acetyl [Leu28Leu31] NPY 24-36 significantly increased it. These findings suggest a role for NPY Y1 receptors in pathways mediating decreases in ventilation and blood pressure, and for NPY Y2 receptors in those mediating increased ventilation and blood pressure.     

Central effects of leptin on cardiovascular and neurohormonal responses in conscious rabbits

We determined the cardiovascular and neurohormonal responses to intracerebroventricular injection of leptin in conscious rabbits. Intracerebroventricular injection of leptin elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity while producing no consistent, significant increases in heart rate. Peak values of mean arterial pressure and renal sympathetic nerve activity induced by intracerebroventricular injection of 50 microgram of leptin (+17.3 +/- 1.2 mmHg and +47.9 +/- 12.0%) were obtained at 10 and 20 min after injection, respectively. Plasma catecholamine concentrations significantly increased at 60 min after intracerebroventricular injection of leptin (control vs. 60 min; epinephrine: 33 +/- 12 vs. 97 +/- 27 pg/ml, P < 0.05; norepinephrine: 298 +/- 39 vs. 503 +/- 86 pg/ml, P < 0.05). Intracerebroventricular injection of leptin also caused significant increases in plasma vasopressin and glucose levels. However, pretreatment with intravenous injection of pentolinium (5 mg/kg), a ganglion blocking agent, abolished these cardiovascular and neurohormonal responses. On the other hand, intravenous injection of the same dose of leptin (50 microgram) as used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. These results suggest that intracerebroventricular leptin acts in the central nervous system and activates sympathoadrenal outflow, resulting in increases in arterial pressure and plasma glucose levels in conscious rabbits.