Biomedical subjects

G Ballejo

Publications and source records attributed to G Ballejo.

At least 19 recordsLinked to original sources

PubMed2006

Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors.

Cholecystokinin (CCK) influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95% CI: 4.1-152 nM) and cerulein (EC50: 58; 95% CI: 18-281 nM) induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG) reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95% CI: 2.5-18 microM) in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 microM L-NOARG from 73 +/- 5.1 to 19 +/- 3.5% in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.

Animals↗

PubMed2004

Role of spinal nitric oxide synthase-dependent processes in the initiation of the micturition hyperreflexia associated with cyclophosphamide-induced cystitis.

The aim of this study was to examine the participation of nitrergic neurotransmission in the initiation of micturition hyperreflexia associated to cyclophosphamide (CP)-induced cystitis in rats. Micturition threshold volume was significantly reduced 4 h after CP administration (100 mg/kg, i.p.); this reduction was attenuated by intra-arterially injected N(G)-nitro-l-arginine-methyl ester (l-NAME), a non selective nitric oxide synthase (NOS) inhibitor, but not by intravesical infusion of S-methyl-l-thiocitrulline (l-SMTC), another structurally different NOS inhibitor. Interestingly, l-NAME failed to affect micturition threshold volume in normal rats. The magnitude of isolated detrusor strips contractions elicited by either carbachol or nerve activation was significantly reduced in CP-treated rats but was unaffected by the addition of N(G)-nitro-l-arginine (l-NOARG), a nonselective NOS inhibitor. In contrast, intrathecal l-NAME and l-SMTC but not N(G)-nitro-d-arginine-methyl ester (d-NAME) administration augmented the micturition threshold volume in CP-treated rats in an l-arginine preventable manner. As with the systemic injection, intrathecal l-NAME also did not affect the micturition threshold volume in normal rats. Four hours after CP injection, the number of neuronal NOS immunoreactive or nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) positive neurons in spinal lumbosacral segments (L6-S2) was not altered whereas the number of c-Fos immunoreactive neurons increased significantly in the dorsal gray commissural nucleus (DGC), the parasympathetic sacral nucleus (PSN) and lamina X of these segments. Ca(2+)-dependent, but not Ca(2+)-independent NOS activity increased significantly in spinal L6-S2 segments but not in thoracic segments of CP-treated rats. These data indicate that the micturition hyperreflexia observed in the initial hours of CP-induced cystitis is associated with an increase in Ca(2+)-dependent NOS activity in spinal L6-S2 segments suggesting an increased production of nitric oxide (NO). The increased production of NO in these spinal segments appears to be necessary for the initiation of the micturition hyperreflexia.

Animals↗

PubMed2001

Cardiac sympathetic overactivity and decreased baroreflex sensitivity in L-NAME hypertensive rats.

The present study evaluated the possible changes in the autonomic control of heart rate in the hypertensive model induced by the inhibition of nitric oxide synthase. Rats were treated with N(G)-nitro-L-arginine methyl ester (L-NAME group) in the drinking water during 7 days, whereas control groups were treated with tap water (control group) or with the N(G)-nitro-D-arginine methyl ester (D-NAME group), an inactive isomer of the L-NAME molecule. The L-NAME group developed hypertension and tachycardia. The sequential blockade of the autonomic influences with propranolol and methylatropine indicated that the intrinsic heart rate did not differ among groups and revealed a sympathetic overactivity in the control of heart rate in the L-NAME group. The spectral density power of heart rate, calculated using fast-Fourier transformation, indicated a reduced variability in the low-frequency band (0.20-0.60 Hz) for the L-NAME group. The baroreflex sensitivity was also attenuated in these animals when compared with the normotensive control or D-NAME group. Overall, these data indicate cardiac sympathetic overactivity associated with a decreased baroreflex sensitivity in L-NAME hypertensive rats.

Animals↗

PubMed2000

Pharmacological profile of nitrergic nerve-, nitric oxide-, nitrosoglutathione- and hydroxylamine-induced relaxations of the rat duodenum.

Activation of inhibitory nonadrenergic noncholinergic (NANC) nerves in the rat duodenum cause relaxations, which are reduced by nitric oxide synthase (NOS) inhibitors indicating that this response involves a nitrergic neurotransmission. The precise nature of the nitrergic neurotransmitter is still controversial since nitric oxide (NO) scavengers and superoxide generators, even in the presence of superoxide dismutase inhibitors, failed to inhibit nitrergic neurotransmission mediated relaxations. In order to understand the role of NOS in nitrergic neurotransmission and considering that N-OH-arginine (OH-L-Arg), L-citrulline, NO, S-nitrosoglutathione (GSNO) and hydroxylamine (NH2OH) can be formed in cells during the N(G)-oxidation of L-arginine catalyzed by NOS we explored whether any of these products could exhibit biological properties comparable to those of the nitrergic neurotransmitter. After establishing which of them was able to relax the rat duodenum, the pharmacological profile of such effect was determined employing oxyhemoglobin (OxyHb), pyrogallol (PYR), hydroquinone (HQ), hydroxocobalamin (HC) or carboxy-PTIO (C-PTIO) and compared with that of nerve mediated relaxations. NO, GSNO and NH2OH, but not OH-L-ARG and L-citrulline, caused concentration-dependent relaxations that were not affected by tetrodotoxin or L-NOARG. OxyHb almost abolished NO-induced relaxations but decreased only marginally the magnitude of nerve-, NH2OH- and SNG-induced relaxations. PYR, HQ and C-PTIO reduced significantly GSNO- and NO- induced relaxations but did not affect those induced by NH2OH or nerve activation. In contrast, HC abolished NO-induced relaxations while it did not affect those induced by GSNO, NH2OH and nerve activation. The catalase inhibitor 1,2,4 aminotriazole failed to affect nerve and NH2OH induced relaxations. These findings indicate that among the products that can be formed during NOS catalyzed L-arginine N(G)-oxidation, only NH2OH caused relaxations that exhibited a pharmacological profile similar to those induced by the nitrergic neurotransmitter. Furthermore, if NH2OH is the actual neurotransmitter it appears to be acting either directly or by a catalase independent release of NO.

Animals↗

PubMed1999

Effect of hydroquinone, hydroxocobalamin and carboxy-PTIO on non-adrenergic non-cholinergic nerve mediated relaxations of the rat duodenum.

Relaxation induced by NANC-nerve stimulation is reduced by nitric oxide synthase (NOS) inhibitors but not by superoxide generators or NO scavengers, casting doubts on the precise nature of the neurotransmitter being released by these nerves. The lack of effect of superoxide anion generators to inhibit nitrergic nerve-mediated relaxations has been attributed to the protective action of high tissue levels of superoxide dismutase (SOD). The effects of hydroquinone, hydroxocobalamin and carboxy-PTIO, three NO inactivators which do not depend on superoxide anion generation, upon nitrergic nerve-mediated relaxations of the rat proximal duodenum were determined in order to elucidate whether they are mediated by free NO. GABA and nicotine caused relaxations of isolated segments of the rat proximal duodenum in a concentration-dependent manner that were abolished by tetrodotoxin (TTX). Similarly, transmural electrical stimulation (TES) caused frequency-dependent relaxations that were also abolished by TTX. The NOS inhibitors L-NAME and L-NOARG reduced in a concentration-dependent manner nerve-mediated relaxations elicited by TES, nicotine and GABA. The effect of NOS inhibitors was prevented by L-arginine but not D-arginine. NO caused concentration-dependent relaxations that were not affected by TTX or L-NOARG but were abolished by hydroquinone, hydroxocobalamin and carboxy-PTIO. In contrast, these compounds failed to affect TES-, nicotine- and GABA-induced relaxations. The lack of effect of hydroquinone, hydroxocobalamin and carboxy-PTIO upon nerve-mediated relaxations was unaltered by pretreatment with the SOD irreversible inhibitor DETCA. The present findings show that nitrergic nerve-mediated relaxations of the rat duodenum are unaffected by NO inactivators that do not generate superoxide anion. It is suggested that either a NO-containing molecule that is unreactive with the inactivators tested is the inhibitory neurotransmitter released by nitrergic nerves or that NOS activity fulfills another role in nitrergic nerves which could be related to the release of an still unidentified transmitter.

Animals↗

PubMed1999

Isolation and characterization of an arginine ester hydrolase from Bothrops jararacussu venom which induces contractions of the isolated rat uterus.

The isolation and partial characterization of a serine protease with arginine ester hydrolase activity from Bothrops jararacussu snake venom are described. The purification procedure consisted of a gel filtration of the crude venom on Sephadex G-75 followed by an ion-exchange chromatography of the active fraction on DEAE-cellulose and a rechromatography on Bio-Rex 70 resin. The esterase fraction (DI-III), M(r) = 25,000 by SDS-PAGE, showed proteolytic activity on fibrinogen and casein. After 2 hr incubation, the A alpha and B beta chains of fibrinogen were intensely hydrolysed, while the gamma chain kept apparently intact, even after 20 hr of incubation. In spite of that, DI-III did not clot fibrinogen. DI-III induced edema in the rat paw. Although unable to release bradykinin, it induced contractions of the isolated rat uterus. DI-III did not catalyse the hydrolysis of bradykinin. Its arginine ester hydrolase activity was completely inhibited by diisopropyl fluorophosphate after 1 hr incubation, but not by phenylmethylsulfonyl fluoride under the same conditions.

Animals↗

PubMed1999

Power spectra of arterial pressure and heart rate in streptozotocin-induced diabetes in rats.

BACKGROUND: Chronic diabetes is associated with alterations in autonomic modulation of the cardiovascular system. Although the rat has been used extensively in studies of experimental diabetes, there have been no reports on the changes in autonomic modulation of the cardiovascular function in chronic diabetic rats. OBJECTIVE: To examine chronic diabetic rats to determine the autonomic modulation of arterial pressure and heart rate variabilities in the time and frequency domain. MATERIALS AND METHODS: Diabetes was induced in rats by a single injection of streptozotocin, and 30 min of pulsatile arterial pressure was recorded in conscious rats, 5, 10-20 days and 12-18 weeks after the streptozotocin injection. Control rats were injected with vehicle. Beat-by-beat systolic arterial pressure and heart rate were obtained from pulsatile pressure. The spectral density powers of systolic arterial pressure and heart rate were calculated using fast Fourier transformation, and integrated in low-(0.015-0.25 Hz), mid- (0.25-0.75 Hz) and high- (0.75-3.0 Hz) frequency bands. The standard deviations of systolic arterial pressure and heart rate were also calculated. RESULTS: Basal systolic arterial pressure and heart rate were reduced in diabetic animals studied 10-20 days and 12-18 weeks after the streptozotocin injection. The standard deviations of systolic arterial pressure and heart rate were also reduced in the chronically diabetic animals. Diabetes reduced low- and mid-frequency variability but not the high-frequency variability of systolic arterial pressure. The low-frequency variability, but not the mid-frequency variability, of the heart rate was also reduced, while the high-frequency variability of the heart rate was reduced in the more chronically diabetic rats. CONCLUSION: Our findings that the mid-frequency band variability of arterial pressure was reduced in diabetic patients suggest that sympathetic modulation of the cardiovascular system is impaired, corroborating other studies in such patients using this and other approaches.

Animals↗

PubMed1998

Mechanism of neuromuscular blockade induced by phenthonium, a quaternary derivative of (-)-hyoscyamine, in skeletal muscles.

1. The mechanisms underlying the postjunctional blockade induced by phenthonium [N-(4-phenyl) phenacyl 1-hyoscyamine] were investigated in mammalian and amphibian muscles. This muscarinic antagonist was previously shown to enhance specifically the spontaneous acetylcholine (ACh) release at concentrations that blocked neuromuscular transmission. 2. In both rat diaphragm and frog sartorius muscles, phenthonium (Phen, 1-100 microM) depressed the muscle twitches elicited by nerve stimulation (IC50: 23 microM and 5 microM, respectively), and blocked the nerve-evoked muscle action potential. The neuromuscular blockade was not reversed after incubation with neostigmine. 3. Equal concentrations of Phen decreased the rate of rise and prolonged the falling phase of the directly elicited action potential in frog sartorius muscle fibres, indicating that the drug also affects the sodium and potassium conductance. 4. Phen (50 and 100 microM) protected the ACh receptor against alpha-bungarotoxin (BUTX) blockade in the mouse diaphragm allowing recording of endplate potentials and action potentials after 5 h wash with physiological salt solution. 5. Phen (10-100 microM) produced a concentration- and voltage-dependent decrease of the endplate current (e.p.c.), and induced nonlinearity of the current-voltage relationship. At high concentrations Phen also shortened the decay time constant of e.p.c (tau(e.p.c.)) and reduced its voltage sensitivity. 6. At the same range of concentrations, Phen also reduced the initial rate of [125I]-BUTX binding to junctional ACh receptors of the rat diaphragm (apparent dissociation constant = 24 microM), the relationship between the degree of inhibition and antagonist concentration being that expected for a competitive mechanism. 7. It is concluded that Phen affects the electrical excitability of the muscle fibre membrane, and blocks neuromuscular transmission through a mechanism that affects the agonist binding to its recognition site and ionic channel conductance of the nicotinic ACh receptor.

Animals↗

PubMed1998

In vitro and in vivo effects of nitric oxide synthase inhibitors and nitric oxide inactivators on the South American opossum ileocolonic junction.

The potential role of nitrergic nerves in the regulation of the South American (SA) opossum ileocolonic junction (ICJ) function was investigated. In vitro, the effects of nitric oxide (NO) synthase inhibitors and NO inactivators on the non-adrenergic non-cholinergic (NANC) nerve-mediated relaxations of the circular muscle of the SA opossum ICJ were determined by employing isolated strips. Electrical field stimulation (0.2-8.0 Hz) caused frequency-dependent NANC relaxations. Nicotine and ATP also induced concentration dependent NANC relaxations that were abolished by tetrodotoxin (TTX). The relaxation response induced by NANC nerve activation was reduced in a dose dependent manner by NO synthase inhibitors while vasoactive intestinal peptide (VIP) and sodium nitroprusside (SNP) induced relaxations were uninfluenced by these drugs. In vivo, the NO synthase inhibitor, L-NAME, administered into the local artery caused a raise in intraluminal pressure of the ICJ in anaesthetized SA opossums in a L-arginine-preventable manner. Hydroquinone and pyrogallol, while being able to reduce, in a superoxide dimutase (SOD) reversible manner, the relaxations induced by exogenous NO failed to affect the NANC nerve-induced relaxations. Finally, neurones and nerve fibres in the myenteric plexus as well as varicose nerve fibres on the circular smooth layer were positive for NADPH-diaphorase activity. These findings indicate that nitrergic nerves inhibit ICJ circular smooth muscle in vitro and in vivo but cast doubts on the neuromediator being the NO radical.

Animals↗

PubMed1998

Role of non-nitric oxide non-prostaglandin endothelium-derived relaxing factor(s) in bradykinin vasodilation.

The most conspicuous effect of bradykinin following its administration into the systemic circulation is a transient hypotension due to vasodilation. In the present study most of the available evidence regarding the mechanisms involved in bradykinin-induced arterial vasodilation is reviewed. It has become firmly established that in most species vasodilation in response to bradykinin is mediated by the release of endothelial relaxing factors following the activation of B2-receptors. Although in some cases the action of bradykinin is entirely mediated by the endothelial release of nitric oxide (NO) and/or prostacyclin (PGI2), a large amount of evidence has been accumulated during the last 10 years indicating that a non-NO/PGI2 factor accounts for bradykinin-induced vasodilation in a wide variety of perfused vascular beds and isolated small arteries from several species including humans. Since the effect of the non-NO/PGI2 endothelium-derived relaxing factor is practically abolished by disrupting the K+ electrochemical gradient together with the fact that bradykinin causes endothelium-dependent hyperpolarization of vascular smooth muscle cells, the action of such factor has been attributed to the opening of K+ channels in these cells. The pharmacological characteristics of these channels are not uniform among the different blood vessels in which they have been examined. Although there is some evidence indicating a role for KCa or KV channels, our findings in the mesenteric bed together with other reports indicate that the K+ channels involved do not correspond exactly to any of those already described. In addition, the chemical identity of such hyperpolarizing factor is still a matter of controversy. The postulated main contenders are epoxyeicosatrienoic acids or endocannabinoid agonists for the CB1-receptors. Based on the available reports and on data from our laboratory in the rat mesenteric bed, we conclude that the NO/PGI2-independent endothelium-dependent vasodilation induced by BK is unlikely to involve a cytochrome P450 arachidonic acid metabolite or an endocannabinoid agonist.

Animals↗

PubMed1997

Nonadrenergic-noncholinergic relaxations of isolated circular muscle from South American opossum esophagogastric junction: is nitric oxide the inhibitory mediator?

Nonadrenergic-noncholinergic (NANC) inhibitory nerves are responsible for most of the nerve induced relaxations of gastrointestinal muscle. It has recently been proposed that NANC nerves may release nitric oxide (NO) or a related compound derived from L-arginine. We have recently shown that the South American (SA) opossum is another suitable model to elucidate the mechanism involved in these NANC relaxations. In the present study the effect of NO synthase inhibitors as well as NO inactivators on the NANC-nerve induced relaxations of the circular muscle of the esophagogastric junction (EGJ) of the SA opossum was investigated. It was observed that the NO synthase inhibitors, L-NOARG and L-NAME, caused a concentration-dependent reduction of NANC-nerve induced relaxations which was reversed by L- but not D-arginine. The NO-donors sodium nitroprusside and hydroxilamine as well as NO caused concentration-dependent relaxations of the EGJ circular muscle. In the myenteric plexus of this region, NADPH-diaphorase positive neurons and nerve fibers were observed while in the circular muscle layer only numerous positive fibers were found. The NO inactivators, hydroquinone, pyrogallol and carboxy-PTIO, reduced NO-induced relaxations but failed to affect NANC nerve- and sodium nitroprusside-induced relaxations. Taken together, these findings indicate that NANC nerve induced relaxation of the SA opossum EGJ circular muscle is dependent on neural NO synthase activity and suggest that the neurotransmitter being released is a superoxide resistant molecule, which is unlikely to be the NO radical, or that the activity of NO synthase is required for the release of the actual neurotransmitter rather than for synthesizing the neuromediator.

Adrenergic beta-Agonists↗

PubMed1997

Novel effects of guanidine on the neuromuscular junction.

1. The effects of guanidine on the isolated mouse phrenic nerve diaphragm (MPND) and chick biventer cervicis (CBC) neuromuscular preparations were determined by myographic and electrophysiological methods. 2. Guanidine at concentrations of 5-10 mM induced an initial facilitation followed by neuromuscular blockade in both preparations. In the isolated MPND such blockade was associated with the abolition of miniature end-plate potentials (MEPPs), but in the CBC the acetylcholine-induced contracture remained unimpaired. After guanidine removal, a heretofore undescribed pronounced facilitation of neuromuscular transmission associated with an increase in MEPP frequency was observed. Simultaneously, the muscular contractions exhibited delayed relaxation and aftercontractions. 3. The K+ channel opener, cromakalim (100-200 microM) inhibited both the well-described initial and the novel postremoval facilitatory effects of guanidine in a concentration-dependent manner. These findings are consistent with the proposal that guanidine blocks K+ channels in motor nerve endings. 4. The guanidine-induced NMB was reverted by increasing the Ca2+ concentration (1.8-5 mM) in the nutritive solution. 5. Tetrodotoxin (TTX, 1.56 microM) did not influence the increase in MEPPS frequency induced by guanidine (10 mM) but did reduce the rise in MEPPS frequency observed after guanidine removal. 6. The present findings indicate that the effects of guanidine on the neuromuscular junction are more complex than currently described because they include a neuromuscular blockade and a post-removal facilitation previously unreported in the literature.

4-Aminopyridine↗

PubMed1997

Influence of sympathetic blockade on the acute hypertensive response to aortic constriction.

The objective of the present study was to determine the contribution of the sympathetic nervous system to the hypertensive response to acute (45-min) aortic coarctation in conscious intact or sinoaortic-denervated (SAD) rats. Rats were treated chronically (5 wk) with guanethidine (50 mg.kg-1.day-1 i.p.) to induce sympathetic nerve degeneration or acutely with the alpha 1-adrenergic receptor antagonist prazosin. (1 mg/kg i.v.). Aortic constriction elicited a prompt and sustained rise in mean carotid pressure that was significantly greater in SAD than in intact rats. The increase in pressure was associated with reflex bradycardia only in the intact rats, whereas the heart rate of SAD rats did not change. Guanethidine treatment did not affect the arterial pressure or heart rate responses to aortic coarctation of intact rats but blunted the hypertensive response of SAD rats to the same values exhibited by intact rats. Prazosin administered 10 min after the beginning of aortic coarctation reduced the hypertensive response of SAD rats to the same level as that of intact rats. In conclusion, the data obtained by means of the association of sinoaortic deafferentation with chronic sympathectomy with guanethidine or acute alpha 1-adrenergic receptor blockade with prazosin indicate that the greater hypertensive response of SAD rats involves a lack of suppression of the sympathetic activity in the maintenance of the rise in pressure elicited by aortic coarctation.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1997

Nitric oxide blunts sympathetic response of pregnant normotensive and hypertensive rat arteries.

Rat pregnancy is associated with a blunted response to vasocontrictors both in vivo and in vitro as well as a decrease in arterial pressure. We examined the influence of pregnancy on neurally induced vasoconstrictor and vasodilator responses of the isolated mesenteric arterial bed from normotensive Wistar and spontaneously hypertensive nonpregnant and 20-day pregnant rats and determined the possible role of nitric oxide (NO) in modulating these responses. MAP (mm Hg) in pregnant normotensive (98+/-1, n=13) and hypertensive (136+/-5, n=13) rats was lower (P<.05) than in nonpregnant controls (114+/-2, n=14, and 174+/-3, n=12, respectively). In isolated mesenteric arterial beds, electrical field stimulation (EFS; 34 V, 3 ms, 10-64 Hz) of perivascular nerves at basal tone induced a frequency-dependent increase in perfusion pressure that was significantly (P<.001) greater in preparations from hypertensive compared with normotensive rats. Pregnancy was associated with a significant decrease in the maximal vasoconstrictor response elicited by EFS in both normotensive and hypertensive groups compared with their nonpregnant controls. In phenylephrine-preconstricted mesenteric beds, EFS (60 V, 1 ms, 1-8 Hz) elicited a similar frequency-dependent decrease in perfusion pressure in normotensive and hypertensive groups, but pregnancy did not influence these responses. In the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine (200 micromol/L), the maximal vasoconstrictor response induced by EFS was significantly (P<.001) augmented in both normotensive and hypertensive groups, and the differences observed between pregnant and nonpregnant groups were abolished. Responses to sodium nitroprusside were not affected by pregnancy, although they were greater in preparations from hypertensive rats. These results indicate that NO contributes to pregnancy-associated diminished vasoconstrictor response to sympathetic stimulation in the mesenteric arterial bed of both normotensive and hypertensive rats.

Animals↗

PubMed1997

Heart rate variability and baroreceptor function in chronic diabetic rats.

In conscious chronic (12 to 18 weeks) streptozotocin diabetic rats, we examined the changes in basal heart rate, with particular attention to heart rate variability assessed by evaluating the standard deviation (bpm) of the lengths of adjacent pulse pressure. We also investigated in anesthetized rats the ability of the aortic baroreceptors to acutely (30 minutes) reset to hypertensive levels. For this purpose, pressure-nerve activity curves for the baroreceptors were obtained, and gain (slope of the curve) and mean arterial pressure at 50% of maximal baroreceptor activity were calculated. The shift of the pressure-nerve activity curve was used as an index of resetting. Conscious diabetic rats (n=6) exhibited lower mean arterial pressure (93+/-6 versus 109+/-4 mm Hg), heart rate (272+/-25 versus 359+/-11 bpm), and heart rate variability (18+/-7 versus 36+/-6 bpm) than control rats (n=7). Under anesthesia, diabetic rats (n=7) and control rats (n=8) exhibited similar mean arterial pressure (113+/-6 versus 109+/-7 mm Hg in control rats ), mean arterial pressure at 50% of maximal baroreceptor activity (117+/-5 versus 107+/-6 bpm), gain (1.66+/-0.08 versus 1.81+/-0.05%/mm Hg), and extent of resetting (44+/-12 versus 49+/-9%) to hypertensive levels. The present study demonstrated that conscious chronic diabetic rats presented lower heart rate variability than control rats. On the other hand, chronic diabetes was not associated with alterations in baroreceptor function or its ability to rapidly reset to hypertensive levels.

Animals↗

PubMed1997

Characterization of nerve-induced relaxation of gastrointestinal sphincteric smooth muscle in a South American opossum (Didelphis albiventris).

The presence of inhibitory nonadrenergic noncholinergic (NANC) intrinsic innervation of the circular muscle of the gastrointestinal sphincters of the South American (SA) opossum was investigated in vitro. Isolated circular muscle strips from the esophagogastric and ileocolonic junctions but not from the gastroduodenal(pylorus)region developed spontaneous tension. Tetrodotoxin (TTX, 1 microM) augmented the spontaneous tension only in the ileocolonic junction strips. Electrical field stimulation of esophagogastric and ileocolonic junction strips caused frequency-dependent responses consisting of a relaxation at lower frequencies (< 1 Hz) and a biphasic response or contraction field stimulation abolished the spontaneous activity at lower frequencies and induced contractions at higher frequencies. The responses elicited by electrical field stimulation in the three sphincters were abolished by TTX (1 microM). Electrical field-induced contractions were reduced while relaxations were enhanced by atropine (1 microM). In the presence of atropine (1 microM) and guanethidine (3 microM), electrical field stimulation, nicotine and ATP induced frequency- or concentration-dependent relaxations of the three sphincters that were abolished by TTX (1 microM). Isoproterenol and sodium nitroprusside caused concentration-dependent relaxations which were TTX-resistant. These findings indicate that the sphincteric circular muscle of the SA opossum gastrointestinal tract is relaxed by the activation of intrinsic NANC nerves and therefore can be used as a model for the study of the mechanisms involved in these responses.

Animals↗

PubMed1997

Involvement of nitric oxide in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis.

The involvement of nitric oxide (NO) and the potential modulation of NO synthase (NOS) activity by platelet-activating factor were investigated in a rat model of cyclophosphamide-induced hemorrhagic cystitis. Male Wistar rats received a single intraperitoneal injection of cyclophosphamide, and cystitis was evaluated 6, 12, 24, 48, and 72 hours later by determining the changes in bladder wet weight and plasma protein extravasation and the macro- and microscopic morphological alterations. In addition, NOS activity and NADPH-diaphorase histochemistry were studied in bladder tissues. Normal bladders showed extensive NADPH-diaphorase staining and a high level of constitutive NOS whereas the activity of inducible NOS was almost undetectable. Cyclophosphamide dose- and time-dependently increased the bladder wet weight and bladder plasma protein extravasation. These events were accompanied at a microscopic level by urothelial necrosis, sloughing, ulceration, hemorrhage, and leukocyte infiltration. Cyclophosphamide also increased the levels of inducible NOS but reduced those of constitutive NOS. The NOS inhibitors L-NG-nitroarginine methyl ester and L-NG-nitroarginine significantly reduced the cyclophosphamide-induced plasma protein extravasation and urothelial damage. This reduction was completely reversed by L-arginine but not by D-arginine. The administration of the platelet-activating factor antagonist BN 52021 decreased the cyclophosphamide-induced plasma protein extravasation as well as the rise in inducible NOS activity but had no effect on the fall in constitutive NOS activity. These results suggest that endogenous NO participates in the urothelial damage and in the inflammatory events leading to cyclophosphamide-induced hemorrhagic cystitis. Platelet-activating factor also seems to be involved in the pathogenesis of this condition, possibly by inducing NOS.

Animals↗

PubMed1996

ANP as a neuroendocrine modulator of body fluid homeostasis.

The role played by the central nervous system (CNS) in the control of body fluid homeostasis has been demonstrated by several authors. The AV3V plays a key role in central control of sodium excretion since its cholinergic, adrenergic, angiotensinergic and osmotic stimulation enhances and its destruction blocks sodium excretion in rats and goats. Cholinergic stimulation of the AV3V induced an increase in plasma ANP as well as a marked elevation in content of the peptide in medial basal hypothalamus, neuro and adenohypophysis. On the other hand, a decline in plasma ANP after AV3V lesions was accompanied by dramatic declines in content of ANP in these same structures. Our previous work has also indicated the essential role of the AV3V region and its ANPergic neurons in the control of ANP release in response to volume expansion (BVE) and indicated that alpha-adrenergic and muscarinic receptors are critical in mediating these responses. Lesions of the AV3V region, or of the median eminence or posterior lobe of pituitary gland blocked the increase in plasma ANP concentration in response to BVE. That this effect is related to blockage of the activity of the brain ANPergic neurons is supported by findings in sheep and in rats that the injection of the antiserum directed against ANP into the AV3V region at least partially blocked the BVE-induced release of ANP. We and others have also previously shown that denervation of baroreceptors inhibits ANP release induced by BVE. Activation of the ANP neurons also cause release of ANP from the anterior and neural lobe of pituitary gland. ANP neurons may activate oxytocinergic neurons in the supraoptic and paraventricular, which projects to neural lobe. Oxytocin would circulate to the atria and may directly activate release of ANP from the atrial myocytes, since i.v. or i.p. injection of oxytocin increases sodium excretion as well as elevates plasma ANP. Oxytocin is present in the neural lobe in large quantity, which could reach the atria myocytes in high concentration and release ANP that circulate to the kidneys and evokes natriuresis to return circulating blood volume to normal.

Animals↗