Sodium reabsorption and the aldosterone receptors in the cells of the kidney tubules in a dynamic disorder of the trophic function of the nervous system]

The results are presented of investigations on determining the functional state of mineralocorticoid receptor apparatus in rat kidney at diverse stages of the reflex renal dystrophy per se and that against the background of renal denervation along with propranolol injections produced at different terms following the disturbance of nervous system trophic function. It was shown that simultaneous blockade of neuroconductory and humoral pathways of pathological stimulus transmission from central end of cut ischiatic nerve to the kidney prevents the development of trophic disturbances in the organ as tested by the state of mineralocorticoid receptors, to a more extent than the blockade of neuroconductory pathway only. The activity of molecular structures which determine the mineralocorticoid reception in cells of renal tubules seems to be controlled both by central neuroconductory and humoral mechanisms.     

Effect of β Adrenoreceptor Blocker Propranolol during Reflex Renal Dystrophy Induced by Sciatic Nerve Cutting

We present the data on the functional status of the mineralocorticoid receptor system in the rat kidney in the course of renal reflex dystrophy induced by sciatic nerve cutting against the background of both renal denervation and injections of propranolol, a -adrenoreceptor blocker. According to the state of renal mineralocorticoid receptors, the simultaneous block of both neural and humoral pathological stimuli coming to the kidney after the nerve injury prevented cytochemical changes in the organ more effectively than the block of neural transmission alone. We propose that both the central neural transmission and humoral mechanisms control the activity of the molecular structures responsible for aldosterone reception in the cells of renal tubules.     

Aldosterone Binding by Compensatory Hypertrophied Kidney with Disturbed Neurotrophic Supply in Rats

We studied certain aspects of interaction between (³H)aldosterone and the cytoplasmic as well as nuclear receptors of renal cells in the rats during compensatory renal hypertrophy at the background of reflex renal dystrophy. The dystrophy developing in the kidney after cutting the sciatic nerve blocks the compensatory increase in specific accumulation of (³H)aldosterone in the cytoplasm of the renal tubular cells. (³H)Aldosterone transport from the cytoplasmic receptors to the nuclear receptors during rat reflex dystrophy of compensatory hypertrophied kidney is lower as compared to the control. The reflex dystrophy induced by a sciatic nerve injury proved to have no effect on the degree of hypertrophy of the only kidney.     

On the Role of β-Adrenoreceptors in Mechanisms Underlying Neurogenic Dystrophies

Sciatic nerve damage led to a defective functioning of the renal mineralocorticoid receptors due to the disturbed neurotrophic supply of this organ: the reception of distorted nervous stimuli. The pharmacological blockade of both the neurotransmitter and the humoral pathways of the pathological stimuli from the damaged nerve to the kidney prevented the development of trophic disturbances as tested by the state of the renal mineralocorticoid receptor system. At the same time, the pharmacological stimulation of the sympathetic nervous system leads to an even more defective aldosterone reception by the kidney. Propranolol exerted an antidystrophic effect in the case of local damages of the nervous system and, thereby, prevented the development of neurogenic dystrophies.     

Cardiac sympathetic nerve stimulation does not attenuate dynamic vagal control of heart rate via alpha-adrenergic mechanism

Complex sympathovagal interactions govern heart rate (HR). Activation of the postjunctional beta-adrenergic receptors on the sinus nodal cells augments the HR response to vagal stimulation, whereas exogenous activation of the presynaptic alpha-adrenergic receptors on the vagal nerve terminals attenuates vagal control of HR. Whether the alpha-adrenergic mechanism associated with cardiac postganglionic sympathetic nerve activation plays a significant role in modulation of the dynamic vagal control of HR remains unknown. The right vagal nerve was stimulated in seven anesthetized rabbits that had undergone sinoaortic denervation and vagotomy according to a binary white-noise signal (0-10 Hz) for 10 min; subsequently, the transfer function from vagal stimulation to HR was estimated. The effects of beta-adrenergic blockade with propranolol (1 mg/kg i.v.) and the combined effects of beta-adrenergic blockade and tonic cardiac sympathetic nerve stimulation at 5 Hz were examined. The transfer function from vagal stimulation to HR approximated a first-order, low-pass filter with pure delay. beta-Adrenergic blockade decreased the dynamic gain from 6.0 +/- 0.4 to 3.7 +/- 0.6 beats x min(-1) x Hz(-1) (P < 0.01) with no alteration of the corner frequency or pure delay. Under beta-adrenergic blockade conditions, tonic sympathetic stimulation did not further change the dynamic gain (3.8 +/- 0.5 beats x min(-1) x Hz(-1)). In conclusion, cardiac postganglionic sympathetic nerve stimulation did not affect the dynamic HR response to vagal stimulation via the alpha-adrenergic mechanism.     

The mineralocorticoid receptor apparatus of the kidneys in rats with reflex dystrophy of the organ against a background of simultaneous denervation or blockade of the body beta-adrenoreceptors by propranolol]

Interaction of labeled aldosterone with rat kidney mineral corticoid cytoplasm receptors and duct cell nuclei at different dysfunctions of nervous-trophic organ supply. Dysfunction of vagus innervation leads to breakage of cytoplasm receptor apparatus and duct cell nuclei that performs aldosterone reception. Organ denervation and introduction of beta-adrenoblocking agent prevents development of kidney neurogenous dystrophy.     

Mechanisms of neurogenic dystrophies induced by activation and deprivation of the sympathetic nervous system

Entry of abnormal nervous stimuli after sciatic nerve transection proved to affect the functioning of renal mineralocorticoid receptors as a result of inadequate neurotrophic support of this organ. Drug blockade of both neural and humoral transmission of the abnormal stimuli from the injured nerve to the kidney prevented development of trophic disorders as indicated by the status of the renal mineralocorticoid receptor system. At the same time, drug stimulation of the sympathetic nervous system further affected aldosterone reception by this organ. -Blocker propranolol was shown to exert an antidystrophic effect in the case of local injuries of the neural system and, thus, prevented the development of neurogenic dystrophies.Translated from Izvestiya Akademii Nauk, Seriya Biologicheskaya, No. 2, 2005, pp. 226–231.Original Russian Text Copyright © 2005 by Akimov, Kositsyn.     

Myocardial ischemia-mediated excitatory reflexes: a new function for thromboxane A2?

Clinical and experimental evidence has shown that myocardial ischemia activates cardiac spinal afferents that mediate sympathoexcitatory reflex responses. During myocardial ischemia, thromboxane A2 (TxA2) is released in large quantities by activated platelets in the coronary circulation of patients with coronary artery disease. We hypothesized that endogenous TxA2 contributes to sympathoexcitatory reflexes during myocardial ischemia through stimulation of TxA2/prostaglandin endoperoxide (TP) receptors. Regional myocardial ischemia was induced by occlusion of a diagonal branch of left anterior descending coronary artery of anesthetized cats. Hemodynamic parameters and renal sympathetic nerve activity were recorded after sinoaortic denervation and bilateral vagotomy. Regional myocardial ischemia evoked significant increases in mean blood pressure (122+/-10 vs. 139+/-12 mmHg, before vs. ischemia), aortic flow (153+/-18 vs. 167+/-20 ml/min), first derivative of left ventricular pressure at 40-mmHg developed pressure (2,736+/-252 vs. 2,926+/-281 mmHg/s), systemic vascular resistance (0.6+/-0.1 vs. 0.9+/-0.12 peripheral resistance units), and renal sympathetic nerve activity (by 22%). The reflex nature of the excitatory responses was confirmed by observing its disappearance after blockade of cardiac nerve transmission with intrapericardial 2% procaine treatment. Moreover, application of U-46619 (2.5-10 microg), a TxA2 mimetic, on the heart caused graded increases in mean arterial pressure and renal nerve activity, responses that were abolished 3 min after local blockade of cardiac neural transmission with intrapericardial procaine. BM 13,177 (30 mg/kg iv), a selective TP receptor antagonist, eliminated the reflex responses to U-46619 and significantly attenuated the excitatory responses during brief (5 min) regional myocardial ischemia. The sympathoexcitatory reflex responses to U-46619 were unchanged by blockade of histamine H1 receptors with pyrilamine and serotonin 5-HT3 receptors with tropisetron, indicating specificity of this TP receptor agonist. These data indicate that endogenous TxA2 participates in myocardial ischemia-mediated sympathoexcitatory reflex responses through a TP receptor mechanism.     

Renorenal reflexes: interaction between efferent and afferent renal nerve activity.

In rats, stimulation of renal mechanoreceptors by increasing ureteral pressure results in a contralateral inhibitory renorenal reflex response consisting of increases in ipsilateral afferent renal nerve activity, decreases in contralateral efferent renal nerve activity, and increases in contralateral urine flow rate and urinary sodium excretion. Mean arterial pressure is unchanged. To study possible functional central interaction among the afferent renal nerves and the aortic and carotid sinus nerves, the responses to renal mechanoreceptor stimulation were compared in sinoaortic denervated rats and sham-denervated rats before and after vagotomy. In contrast to sham-denervated rats, there was an increase in mean arterial pressure in response to renal mechanoreceptor stimulation in sinoaortic-denervated rats. However, there were no differences in the renorenal reflex responses among the groups. Thus, our data failed to support a functional central interaction among the renal, carotid sinus, and aortic afferent nerves in the renorenal reflex response to renal mechanoreceptor stimulation. Studies to examine peripheral interaction between efferent and afferent renal nerves showed that marked reduction in efferent renal nerve activity produced by spinal cord section at T6, ganglionic blockade, volume expansion, or stretch of the junction of superior vena cava and right atrium abolished the responses in afferent renal nerve activity and contralateral renal function to renal mechanoreceptor stimulation. Conversely, increases in efferent renal nerve activity caused by thermal cutaneous stimulation increased basal afferent renal nerve activity and its responses to renal mechanoreceptor stimulation. These data suggest a facilitatory role of efferent renal nerves on renal sensory receptors.     

Modulation of cardiovascular excitatory responses in rats by transcutaneous magnetic stimulation: role of the spinal cord.

This study investigated the efficacy of magnetic stimulation on the reflex cardiovascular responses induced by gastric distension in anesthetized rats and compared these responses to those influenced by electroacupuncture (EA). Unilateral magnetic stimulation (30% intensity, 2 Hz) at the Jianshi-Neiguan acupoints (pericardial meridian, P 5-6) overlying the median nerve on the forelimb for 24 min significantly decreased the reflex pressor response by 32%. This effect was noticeable by 20 min of magnetic stimulation and continued for 24 min. Median nerve denervation abolished the inhibitory effect of magnetic stimulation, indicating the importance of somatic afferent input. Unilateral EA (0.3-0.5 mA, 2 Hz) at P 5-6 using similar durations of stimulation similarly inhibited the response (35%). The inhibitory effects of EA occurred earlier and were marginally longer (20 min) than magnetic stimulation. Magnetic stimulation at Guangming-Xuanzhong acupoints (gallbladder meridian, GB 37-39) overlying the superficial peroneal nerve on the hindlimb did not attenuate the reflex. Intravenous naloxone immediately after termination of magnetic stimulation reversed inhibition of the cardiovascular reflex, suggesting involvement of the opioid system. Also, intrathecal injection of delta- and kappa-opioid receptors antagonists, ICI174,864 (n=7) and nor-binaltorphimine (n=6) immediately after termination of magnetic stimulation reversed inhibition of the cardiovascular reflex. In contrast, the mu-opioid antagonist CTOP (n=7) failed to alter the cardiovascular reflex. The endogenous neurotransmitters for delta- and kappa-opioid receptors, enkephalins and dynorphin but not beta-endorphin, therefore appear to play significant roles in the spinal cord in mediating magnetic stimulation-induced modulation of cardiovascular reflex responses.     

Effect of the sciatic nerve blockade on the function of the contralateral motor center in the rat gastrocnemius muscle

When the rat spinal motor centre was activated by fixing the animal in a supine posture, the motor units of intact gastrocnemius muscle fired more frequently in the high-frequency range. Under conditions of the ischiatic nerve blockade, a shift to an increase in the background firing frequency of the motor units related to intact gastrocnemius muscle seems to be related to increased motoneurone excitability occurring because of the contralateral denervation.     

室旁核在剌激猫肾神经传入纤维引起的血压效应中的应用

The purpose of this study is to investigate the role of paraventricular nucleus of the hypothalamus (PVN) and alpha 1 adrenergic receptor of PVN in the pressor responses to stimulation of renal afferent nerve in alpha 1-chloralose-anesthetized cats with carotid sinoaortic denervation and vagotomy. The pressor response to stimulation of renal afferent nerve consisted of a primary and a second components. The primary component response was completely blocked while the second component was not blocked by autonomic blocking agents (hexomethonium and atropine). Bilateral lesions of PVN greatly attenuated the pressor response before and after autonomic blockade. Intracerebroventricular and PVN injection alpha 1, adrenergic antagonist (prazosin) significantly decreased in the pressor response to stimulation of renal afferent nerve. These results indicate that paraventricular nucleus of the hypothalamus and alpha 1 adrenergic receptors in central nervous system, especially in PVN, play an important role in the pressor responses to stimulation of renal afferent nerve.     

Effect of cardiac receptor stimulation on renal vascular resistance in the pregnant rat

Stimulation of cardiac receptors (CR) evokes blunted reflex reductions in mean arterial pressure (MAP) in pregnant compared with virgin rats. Because CR-mediated sympathoinhibition has preferential effects on the kidney, we tested whether, during pregnancy, renal vascular resistance (RVR) changes less in response to CR stimulation and investigated possible mechanisms. MAP, right atrial pressure, renal sympathetic nerve activity (RSNA), renal blood flow (RBF), and RVR were measured in anesthetized animals in response to CR stimulation by graded atrial injections of saline. Baseline MAP and RVR and reflex changes in these variables during CR stimulation were reduced in late-pregnant vs. virgin rats (P<0.05). Reflex changes in RSNA were attenuated in pregnant rats, but changes in RBF as a function of RSNA were similar in both groups. ANG II AT(1)-receptor blockade increased basal RBF more in virgin rats (P<0.05), but between-group differences in reflex changes in MAP, RSNA, and RVR were maintained after AT(1) blockade. Thus during CR simulation, reflex changes in RVR were reduced in pregnant versus virgin rats. This difference does not appear to involve differential effects of ANG II.     

Neural activation of alpha-adrenoreceptors in glucose mobilization from liver.

Using a newly described method for obtaining pure, mixed hepatic venous blood samples, it was demonstrated that glucose mobilization from the liver of the anesthetized cat in response to hepatic nerve stimulation is via alpha-adrenergic receptors. Neither the elevation of portal pressure nor the amount of glucose generated by the liver was affected by intraportal administration of 1 mg propranolol/kg (beta blockade). In the presence of alpha-receptor blockade (3 mg phentolamine/kg) the portal venous pressure change was minor and the glucose output actually decreased slightly upon nerve stimulation, a response consistent with our previously demonstrated reduction of glucose output by parasympathetic nerve stimulation. The present responses to nerve stimulation were not due to activation of pancreatic nerves since these nerves were routinely ligated.     

Excretory function after unilateral renal denervation and administration of propranolol to unanaesthetized dogs

The experiments were carried out on female dogs with exteriorized ureters prior to and following surgical denervation of the left kidney. Propranolol 1.0 mg/kg b.w. was administered intravenously. Sodium, potassium, chloride, calcium, magnesium, zinc, copper, creatinine and urea concentrations in the urine from the denervated and intact kidneys as well as in blood drawn were determined. After renal denervation PAH clearance was determined. As a result of denervation diuresis and calcium and copper excretion were increased while urine osmolality was diminished. No change occurred in kidney blood flow and GFR. After propranolol administration diuresis, calcium and copper excretion in the intact kidney significantly increased. Changes in the excretory function of the left kidney following its denervation were not a result of alterations in renal haemodynamics. Results obtained indicative of that beta-adrenergic receptors contribute to the excretion of calcium and copper ions.     

Propranolol induces acute natriuresis by beta blockade and dopaminergic stimulation.

dl-Propranolol (0.8-1.6 mg/kg - h for 1 h) produced a transient two- to three-fold increase in sodium excretion in nondiuretic rats infused with Pitressin and aldosterone and in water diuretic rats. Sodium excretion increased more in rats depleted of renin by chronic Doca and salt administration than in rats maintained on a low salt diet. An angiotensin inhibitor (1,sarcosine-8,valine angiotensin II) decreased sodium excretion. Therefore the natriuresis was not mediated by antidiuretic hormone, aldosterone, or renin-angiotensin. d-Propranolol did not produce a natriuresis. Prior treatment with phenoxybenzamine did not prevent the natriuretic response but chlorisondamine pretreatment did. The natriuresis is produced by beta blockade and requires post ganglionic nerve function but is independent of alpha receptors. dl-Propranolol decreased heart rate and cardiac output but systemic pressure did not fall and renal blood flow increased. This suggests a dopamine-mediated renal vasodilation and natriuresis. Haloperidol and pimozide, both dopamine blocking agents with minimal beta blocking effects, prevented the natriuretic response. We conclude that propranolol may increase sodium excretion directly by blocking beta receptors in the distal nephron and indirectly by dopamine-mediated renal vasodilation.     

Absence of alpha-2 adrenergic effects on cAMP production in a genital tract smooth muscle cell line

This study sought to evaluate alpha-2 and beta adrenergic modulation of cAMP production in the DDT1 MF-2 transformed smooth muscle myocyte. After stimulation with forskolin or adrenergic agonists with or without subtype specific antagonists, cAMP production was determined. These experiments confirmed an increase of cAMP in response to forskolin, isoproterenol, epinephrine, and norepinephrine; the adrenergic stimulation was inhibited by propranolol. On the other hand, the alpha-2 agonist clonidine did not inhibit cAMP production. Likewise, alpha-2 receptor blockade did not increase cAMP production in response to epinephrine. These studies, therefore, suggest that the DDT1 MF-2 myocyte does not contain a significant population of functional alpha-2 adrenergic receptors.     

Functional disturbances in the nervous structures of the respiratory tract in rats following nitrogen dioxide inhalation

The functional state of rat's airway smooth muscle was not changed after nitrogen dioxide inhalation for 30 days. The smooth muscle contraction increased only at second stimulation of preganglionic nervous fibers. Removal of mucosa or Novocain blockade of receptors decreased control smooth contraction at nerve and muscle fiber stimulation but the repeated stimulation of nerve increased the muscle contraction. The processing of trachea and bronchus preparations by prednisolon (1-10 microg/ml) decreased muscle reactions to 12% only at nerve stimulation. Prednisolon didn't change reactions of preparations with removed or blockaded receptors induced by nerve stimulation, but prednisolon (10 microg/ml) increased contraction at muscle stimulation. The relax effect of prednisolon on airway smooth muscle realizes via tracheobronchial receptors. High doses of prednisolon may direct effect on muscle increasing its contraction.     

Ventromedial hypothalamic stimulation accelerates norepinephrine turnover in brown adipose tissue of rats

To establish a functional link between the ventromedial hypothalamus (VMH) and brown adipose tissue (BAT), effects of electrical stimulation of the VMH and the lateral hypothalamus (LH) on norepinephrine (NE) turnover in the interscapular BAT were examined in rats. Stimulation of the VMH elicited about 3-fold increase in the rate of NE turnover in BAT, whereas stimulation of the LH had no appreciable effects. The effect of VMH stimulation was abolished after sympathetic ganglion blockade or by surgical sympathetic denervation of BAT. It was concluded that there is a sympathetic nerve-mediated connection between the VMH and BAT, and that stimulation of the VMH induces metabolic activation and heat production in BAT through an increase in sympathetic nerve activity.     

Cardiovascular function in anesthetized miniature swine.

Miniature swine anesthetized with pentobarbital were studied with respect to their cardiovascular function under control conditions and in response to catecholamines, baroreceptor inhibition, bilateral vagotomy and vagal nerve stimulation. Measurements included aortic pressure, heart rate, intraventricular pressure and its maximum rate of rise during contraction, carotid blood flow and resistance, femoral blood flow and resistance, and renal blood flow and resistance. The cardiovascular actions of norepinephrine, epiniphrine and isoproterenol were similar to those in other mammals, and the adrenergic receptor mechanisms also were susceptible to blockade with phentolamine or propranolol. Inhibition of the carotid baroreceptors was accompanied by elevation of aortic pressure, reflex bradycardia and increased femoral and renal resistances. Bileteral vagotomy was followed by hypertension, tachycardia and increased renal resistance. Changes in femoral resistance to these procedures differed between the two strains of miniature swine studied. Stimulation of the peripheral end of either vagus nerve was accompanied by bradycardia without hypotension.