Autonomic dysreflexia during sperm retrieval in spinal cord injury: influence of lesion level and sildenafil citrate.

Autonomic dysreflexia (AD) can occur during penile vibratory stimulation in men with spinal cord injury, but this is variable, and the association with lesion level is unclear. The purpose of this study was to characterize the cardiovascular responses to penile vibratory stimulation in men with spinal cord injury. We hypothesized that those with cervical injuries would demonstrate a greater degree of AD compared with men with thoracic injuries. We also questioned whether the rise in blood pressure could be attenuated by sildenafil citrate. Participants were classified as having cervical (n = 8) or thoracic (n = 5) injuries. While in a supine position, subjects were instrumented with an ECG, and arterial blood pressure was determined beat by beat. Subjects reported to the laboratory twice and received an oral dose of sildenafil citrate (25-100 mg) or no medication. Penile vibratory stimulation was performed using a handheld vibrator to the point of ejaculation. At ejaculation during the nonmedicated trials, the cervical group had a significant decrease in heart rate (-5-10 beats/min) and increase in mean arterial blood pressure (+70-90 mmHg) relative to resting conditions, whereas the thoracic group had significant increases in both heart rate (+8-15 beats/min) and mean arterial pressure (+25-30 mmHg). Sildenafil citrate had no effect on the change in heart rate or mean arterial pressure in either group. In summary, men with cervical injuries had more pronounced AD during penile vibratory stimulation than men with thoracic injuries. Administration of sildenafil citrate had no effect on heart rate or blood pressure during penile vibratory stimulation in men with spinal cord injury.     

Potentiation of histamine release by sodium cromoglycate.

Human lung slices passively sensitized with allergic serum released histamine when incubated with specific antigen and anti-IgE but anti-IgG had no effect. Sodium cromoglycate (SCG) inhibited antigen induced histamine release but the dose-response curve was bell-shaped. Inhibition of anti-IgE induced release was linearly related to dose, whereas that induced by anti-IgG was potentiated by increasing doses of SCG. After sensitization with allergic serum in which IgE had been inactivated by heating, specific antigen released little or no histamine but this was potentiated by SCG. It is concluded that SCG inhibits IgE mediated but potentiates IgG mediated allregic reactions thus explaining its characteristic dose-response curve $\text{in vitro}$.     

下丘脑背内侧核在缰核兴奋诱发的心血管反应及腓深神经抑制中的作用

目的 :阐明下丘脑背内侧核 (DMH)在缰核 (Hb)兴奋诱发的心血管反应中的作用及DMH在腓深神经 (DPN)传入冲动调节Hb兴奋诱发的心血管活动中的作用及机制。方法 :脲酯和氯醛糖混合静脉麻醉的家兔 ,电刺激Hb、腓深神经 ,记录股动脉血压及心外膜电图 ,DMH内微量注射受体拮抗剂。结果 :同侧DMH微量注射谷氨酸受体阻断剂Kynurenicacid ,部分取消了电刺激Hb兴奋诱发的升压反应及缺血性心电变化反应。同侧DMH微量注射纳洛酮对腓深神经传入冲动抑制Hb兴奋诱发的上述反应有削弱作用。结论 :DMH及其中的谷氨酸受体参与电刺激缰核兴奋诱发的心血管反应 ,DMH及其中的阿片受体参与了DPN传入冲动对上述心血管反应的抑制作用     

Blood pressure responsiveness to sympathetic agonists in anaesthetised diabetic rats

Chronic diabetes alters sympathetic modulation of the cardiovascular system. In the present work, we examined if the cardiovascular system also demonstrates an impaired responsiveness to sympathetic control. The effects of streptozotocin-induced diabetes on pressure responses to noradrenaline or isoproterenol infusion of diabetic rats in vivo are studied. Systolic and diastolic pressures were recorded through a cannula implanted in the right carotid artery. Increasing doses of noradrenaline or isoproterenol were infused through a catheter implanted in the left jugular vein. The dose-response curves for the effects of noradrenaline on blood pressure were altered in streptozotozin-induced diabetic rats. Noradrenaline induced a statistically significant higher increase of both systolic and diastolic pressure in control than in diabetic rats. The maximum depressor response of systolic pressure to isoproterenol was lower in diabetic than in control animals. Diabetes fully abolishes the effect of beta-adrenoceptor stimulation on diastolic blood pressure. The present results demonstrate that streptozotocin-induced diabetes reduces systolic and diastolic arterial pressure, and diminishes the arterial pressure reactivity to sympathetic stimulation.     

Inhibitory effects of pergolide on peripheral adrenergic neurotransmission in spontaneously hypertensive rats

Intraperitoneal injection of pergolide (12.5–500 μg/kg) produced dose-related and sustained arterial hypotension in anesthetized spontaneously hypertensive rats (SHR) which was accompanied by bradycardia at higher tested doses. During the time frame of hypotension produced by pergolide (50 μg/kg, i.p.), diastolic blood pressure and cardiac rate responses to electrical stimulation of the sympathetic outflow in pithed SHR were attenuated, whereas comparable responses induced by exogenous norepinephrine were unaffected. Pretreatment of SHR with sulpiride abolished pergolide-induced hypotension and prevented its inhibitory effect on neurogenic vasoconstrictor responses. Sulpiride alone had no effect on responses to electrical stimulation or injected norepinephrine. Yohimbine or vagotomy plus atropine did not attenuate the hypotensive effect of pergolide while hexamethonium or pithing reversed it; increments in pressure produced by pergolide after each of the latter interventions were probably mediated by postsynaptic alpha receptors, since vasoconstrictor responses to pergolide (10?100 μg/kg, i.v.) in pithed preparations were attenuated by phentolamine.The data suggest that pergolide lowers arterial blood pressure and cardiac rate by inhibiting peripheral sympathetic nerve function through a dopaminergic mechanism. The probable site of action of pergolide is at presynaptic (neuronal) dopamine receptors which are known to mediate inhibition of neurogenic release of norepinephrine.     

Hypophysial portal blood flow during preganglionic stimulation of the superior cervical ganglion under condition of systemic arterial blood pressure stabilization in rat.

The presence of hypothalamic hormones in the pituitary portal blood is regarded as the principal factor by which the hypothalamus controls pituitary secretion. In contrast to numerous investigations on hypothalamic hormone release, the regulation of the hypophysial-portal blood flow (HPBF) has been scarcely studied. Hypophysial-portal vessels were exposed according to the Worthington's method [1966]. The 10-min blood samples were collected before and during unilateral or alternative bilateral electrical stimulation of the preganglionic fibers of the superior cervical ganglia (SCG). During blood samples collection the stable systemic arterial blood pressure was maintained by a barostat. The HPBF was estimated according to the determination of the hemoglobin in samples of washed and collected blood from the cut pituitary portal vessels. The mean HPBF was 3.5 microliters/min. Electrical stimulation of SCG. did not change HPBF. This indicates that sympathetic efferents do not participate in the regulation of HPBF under conditions of stabilization of the systemic arterial blood pressure.     

Vascular effects of substance P change synaptic responsiveness of cat dorsal horn neurons

The effects of systemically administered substance P were examined on the responses induced by noxious (radiant heat) and non-noxious (air jets) peripheral stimuli in dorsal horn neurons of the feline spinal cord. Substance P produced a significant fall in arterial blood pressure and selectively enhanced responses to noxious heat stimulation. Other vasoactive substances administered systemically caused either selective increases or decreases in noxious heat induced responses which coincided with decreases or increases in systemic arterial blood pressure respectively. It was concluded that the selective neuronal effects of substance P were secondary to changes in vascular perfusion in the area stimulated by the radiant heat source.     

The Effects of Skeletal Muscle Contractions and Paralysis on Physiological Responses to Head Immersion in Pekin Duck

This study investigated whether increases and decreases in pectoral muscle metabolism influence underwater endurance time and cardiovascular responses to head submersion in Pekin ducks. Muscle metabolic rate (anaerobic ATP synthesis) was estimated using ³¹P magnetic resonance spectroscopy, and was manipulated by direct electrical stimulation and by pharmacological paralysis. These manipulations had no significant effect on underwater endurance times or cardiovascular responses to head immersion (heart rate, mean arterial blood pressure). Anaerobic ATP synthesis was not detectable in paralyzed muscle during head immersion, implying that muscle metabolic rate was reduced to less than 10% of normal resting values. Despite this, underwater endurance times were not significantly extended. We conclude that muscle metabolic rate per se does not influence the maximum breath-hold time in this species.     

Baroreceptor influence on a spinal cardiovascular reflex

A stretch of the walls of the thoracic aorta, performed in vagotomized cats without obstructing aortic flow, induces increases in heart rate, myocardial contractility, and arterial pressure. These reflex responses are still present after high spinal section. Cats under chloralose-urethane anesthesia were vagotomized and one carotid sinus was isolated and perfused with arterial blood at constant flow. The contralateral carotid sinus nerve and both aortic nerves were sectioned. A stretch of the walls of the thoracic aorta between the 7th and 10th intercostal arteries induced a reflex increase in mean arterial pressure 29 +/- 2 mmHg (mean +/- SE). Stepwise increases of carotid sinus pressure (CSP) or electrical stimulation of the carotid sinus nerve induced stepwise decreases of this reflex response. At maximal baroreceptor stimulation (CSP 212 +/- 9 mmHg) the reflex response to aortic stretch was reduced by 42%. These experiments show that this spinal cardiovascular reflex is at least partially under the inhibitory control of the baroreceptor input.     

Naturally occurring hypertension in New World nonhuman primates: Potential role of the perifornical hypothalamus

Hypertension is a prominent underlying factor in the genesis of cardiovascular-related morbidity and mortality. A major impediment to the investigation into the causes of the disease is the paucity of naturally occurring animal models of the disease. There is evidence that some species of New World primates spontaneously become hypertensive. We used chronically implanted pressure transducers to assess normally occurring blood pressure and heart rate levels at rest and during routine laboratory procedures in a group of one of these New World primates (Aotus sp.). Resting mean arterial pressure ranged from 72 to 130 mmHg. Three animals were judged to have resting mean arterial pressure levels in the hypertensive range (> or =110 mmHg). In all of the animals, pressor responses to routine laboratory events were exaggerated (average highest mean pressure during 1 min from any session was 97-196 mmHg). Subsequently, the region of the perifornical/lateral hypothalamus known to produce elevated blood pressure and heart rate responses to electrical stimulation was removed, and the blood pressure responses to the laboratory routines were significantly decreased and, in some cases, eliminated. Control lesions in nearby tissue had no effect on these responses. This region may play a critical role in initiating or exacerbating cardiovascular responses that contribute to the development of essential hypertension.     

Respiratory and circulatory effects of parietal pleural afferent stimulation in rabbits.

Respiratory symptoms accompanying pleural diseases combine dyspnea, tachypnea, rapid shallow breathing, and sometimes hypotension. There are no experimental data on the changes in respiratory and circulatory functions elicited by the activation of pleural afferents. After removal of all muscles covering the 5th to 10th intercostal spaces, we investigated in paralyzed, vagotomized rabbits the changes in phrenic discharge, transpulmonary pressure, and systemic arterial pressure in response to an outwardly directed force exerted on the parietal pleura or the local application of solutions containing lactic acid or inflammatory mediators. Mechanical stimulation of the pleura induced an immediate decrease in both integrated phrenic discharge and arterial blood pressure, the responses being positively correlated with the magnitude of force applied on the pleura. No accompanying changes in ventilatory timing, transpulmonary pressure, or heart rate were measured. Lactic acid solution also elicited an inhibition of phrenic activity and a fall in blood pressure. Section of the internal intercostal nerves supplying the stimulated intercostal spaces totally abolished the responses to mechanical stimulation or lactic acid. An inflammatory mixture elicited only modest respiratory and circulatory effects. We concluded that an acute mechanical distension of the parietal pleura as well as its chemical stimulation by lactic acid elicit a marked inhibition of phrenic motoneurons combined to a reduction of the sympathetic outflow to the circulatory system.     

Electrically elicited cardiovascular and respiratory responses from the nucleus tractus solitarii in unrestrained cats

Heart rate, arterial blood pressure and respiratory rate responses to electrical stimulation of the nucleus tractus solitarii (NTS) were studied in unanaesthetized freely moving cats. Complex cardiovascular response patterns, mainly pressor responses, were obtained from stimulation of the portion of the NTS rostral to the obex. No significant difference was observed between the effects produced by stimulation of the NTS on the right and on the left side. These results indicate that the rostral portion of the NTS also plays a role in the cardiovascular control, and a functional asymmetry between the two sides does not exist at the level of the NTS.     

The antihypertensive action of arachidonic acid in the spontaneous hypertensive rat and its antagonism by anti-inflammatory agents

Changes in arterial blood pressure and heart rate were observed in the spontaneous hypertensive (SH) rat following the intravenous administration of arachidonic acid, the precursor of prostaglandin E₂ (PGE₂). The pronounced fall in blood pressure and the increase in heart rate induced by arachidonic acid were also observed in SH rats receiving either prostaglandin E₁ (PGE₁) or PGE₂. In SH rats receiving various anti-inflammatory agents the cardiovascular responses to arachidonic acid were inhibited, but the blood pressure responses to the E-type prostaglandins were not altered. The data are interpreted to suggest that cardiovascular changes induced by arachidonic acid are mediated via its conversion to PGE₂.     

Reflex cardiovascular responses originating in exercising muscles of mice.

The cardiovascular responses induced by exercise are initiated by two primary mechanisms: central command and reflexes originating in exercising muscles. Although our understanding of cardiovascular responses to exercise in mice is progressing, a murine model of cardiovascular responses to muscle contraction has not been developed. Therefore, the purpose of this study was to characterize the cardiovascular responses to muscular contraction in anesthetized mice. The results of this study indicate that mice demonstrate significant increases in blood pressure (13.8 +/- 1.9 mmHg) and heart rate (33.5 +/- 11.9 beats/min) to muscle contraction in a contraction-intensity-dependent manner. Mice also demonstrate 23.1 +/- 3.5, 20.9 +/- 4.0, 21.7 +/- 2.6, and 25.8 +/- 3.0 mmHg increases in blood pressure to direct stimulation of tibial, peroneal, sural, and sciatic hindlimb somatic nerves, respectively. Systemic hypoxia (10% O(2)-90% N(2)) elicits increases in blood pressure (11.7 +/- 2.6 mmHg) and heart rate (42.7 +/- 13.9 beats/min), while increasing arterial pressure with phenylephrine decreases heart rate in a dose-dependent manner. The results from this study demonstrate the feasibility of using mice to study neural regulation of cardiovascular function during a variety of autonomic stimuli, including exercise-related drives such as muscle contraction.     

Inhibition of peripheral adrenergic neurotransmission by lergotrile in spontaneously hypertensive rats

Intraperitoneal injection of lergotrile (0.5 mg/kg) produced arterial hypotension and bradycardia for 120 and 90 minutes, respectively, in anesthesized spontaneously hypertensive rats (SHR). During this time frame, lergotrile (0.5 mg/kg, i.p.) greatly attenuated diastolic blood pressure and cardiac rate responses to electrical stimulation (0.062-4 Hz) of the sympathetic outflow in pithed SHR, but had no significant effect on comparable increments in pressure and rate produced by exogenous norepinephrine (0.01–10 μg/kg, i.v.). Pretreatment of SHR with haloperidol (2 mg/kg, i.p.) prevented lergotrile-induced hypotension and partially reversed its inhibitory effect on neurogenic vasoconstrictor responses. Haloperidol alone had no significant effect on baseline arterial blood pressure or responses to sympathetic nerve stimulation. Administration of hexamethonium (20 mg/kg, i.v.) to SHR antagonized the hypotensive response to lergotrile (0.5 mg/kg, i.p.), although hydralazine (2 mg/kg, i.p.) still produced a marked reduction in pressure.These results suggest that lergotrile produces arterial hypotension and bradycardia primarily by inhibiting peripheral sympathetic nerve function through a dopaminergic mechanism. The probable site of action of lergotrile is at presynaptic (neuronal) dopamine receptors which are known to be inhibitory to neurogenic release of norepinephrine.     

Muscle mechanosensitive receptors close to the myotendinous junction of the Achilles tendon elicit a pressor reflex.

Feedback regulation by activation of mechanosensitive afferents in the exercising muscle causes the cardiovascular and sympathetic nerve responses, which follow tension development and are almost identical between static contraction and passive stretch. The precise location of the mechanoreceptors contributing to the exercise pressor reflex, however, remained unknown. To test the hypothesis that the mechanoreceptors will be located around the myotendinous junction to monitor a change in muscle tension than a change in muscle length, we examined the reflex cardiovascular responses to passive stretch of the triceps surae muscle in anesthetized rats with three interventions; systemic injection of gadolinium, cutting the Achilles tendon, and local injection of lidocaine into the myotendinous junction. Gadolinium (42 micromol/kg iv) blunted the increases in heart rate and mean arterial blood pressure during passive stretch by 36 and 22-26%, respectively, suggesting that the reflex cardiovascular responses were evoked by stimulation of muscle mechanosensitive receptors. The cardiovascular responses to passive stretch were not different between the cut Achilles tendon and the intact tendon in the same rats, suggesting that any mechanoreceptors, terminated in the more distal part of the tendon, did not contribute to the reflex cardiovascular responses. Lidocaine (volume, 0.04-0.1 ml) injected into the myotendinous junction blunted the stretch-induced increases in heart rate and mean arterial blood pressure by 37-49 and 27-34%, respectively. We conclude that the muscle mechanosensitive receptors evoking the reflex cardiovascular responses at least partly locate at or close to the myotendinous junction of the Achilles tendon.     

Estrogen attenuates the cardiovascular and ventilatory responses to central command in cats.

Static exercise is well known to increase heart rate, arterial blood pressure, and ventilation. These increases appear to be less in women than in men, a difference that has been attributed to an effect of estrogen on neuronal function. In decerebrate male cats, we examined the effect of estrogen (17beta-estradiol; 0.001, 0.01, 0.1, and 1.0 microg/kg iv) on the cardiovascular and ventilatory responses to central command and the exercise pressor reflex, the two neural mechanisms responsible for evoking the autonomic and ventilatory responses to exercise. We found that 17beta-estradiol, in each of the three doses tested, attenuated the pressor, cardioaccelerator, and phrenic nerve responses to electrical stimulation of the mesencephalic locomotor region (i.e., central command). In contrast, none of the doses of 17beta-estradiol had any effect on the pressor, cardioaccelerator, and ventilatory responses to static contraction or stretch of the triceps surae muscles. We conclude that, in decerebrate male cats, estrogen injected intravenously attenuates cardiovascular and ventilatory responses to central command but has no effect on responses to the exercise pressor reflex.     

Spinal vasopressin modulates the reflex cardiovascular response to static contraction.

Recent evidence has demonstrated that arginine vasopressin (AVP) may modulate primary afferent activity of nociceptors in the dorsal horn of the spinal cord. Because nociceptors are group III and IV afferents, spinal AVP also may modulate the activity of group III and IV afferents that cause reflex cardiovascular responses to muscle contraction. Thus, we compared the pressor (mean arterial pressure), myocardial contractile (dP/dt), and heart rate (HR) responses to electrically induced static contraction of the cat hindlimb before and after lumbar intrathecal (IT) injection (L1-L7) of AVP (n = 9), the V1 receptor antagonist d(CH2)5Tyr(Me)AVP (n = 6), the V2 receptor antagonist d(CH2)5[D-Ile2,Ile4,Ala-NH2(9)]AVP (n = 6), and the V2 agonist [Val4,D]AVP (n = 8). After IT injection of AVP (0.1 or 1 nmol) the pressor and contractile responses to static contraction were attenuated by 55 and 44%, respectively. HR was unchanged. Forty-five to 60 min after AVP injection, the contraction-induced pressor and contractile responses were restored to control levels. V1 receptor blockade augmented contraction-induced increases in mean arterial pressure (36%) and dP/dt (49%) but not HR. V2 receptor blockade had no effect on the cardiovascular response to contraction, whereas selective V2 stimulation attenuated the dP/dt (-20%) and HR (-33%) responses but not the pressor response. These results suggest that AVP attenuates the reflex cardiovascular response to contraction by modulating sensory nerve transmission from contracting muscle primarily via a V1 receptor mechanism in the lumbar spinal cord.     

Effect of paraventricular nucleus lesions on cardiovascular responses elicited by stimulation of the subfornical organ in the rat

It has recently been reported that stimulation of the region of the subfornical organ (SFO) elicits an increase in arterial pressure. However, the mechanisms and forebrain neural circuitry that are involved in this cardiovascular response have not been elucidated. The present study was done in urethane-anaesthetized rats to determine whether selective activation of SFO neurons elicit cardiovascular responses and whether these responses were mediated by a pathway involving the paraventricular nucleus of the hypothalamus (PVH). Stimulation sites which required the lowest threshold current (30 microA) to elicit a pressor response and at which the largest rise in mean arterial pressure (MAP; 22 +/- 2 mmHg) was elicited at a constant current intensity (150 microA) were histologically localized in the region of the SFO. Short (mean peak latency; 4 +/- 2 s) and long (mean peak latency; 61 +/- 8 s) latency increases in MAP were observed during and after electrical stimulation of the SFO, respectively. Cardiac slowing accompanied the short latency pressor response and cardioacceleration was observed in most (57%) of the cases to accompany the late pressor response. Microinjection of L-glutamate into the SFO consistently elicited cardiovascular responses qualitatively similar to those observed during electrical stimulation. Ganglionic blockade abolished the short latency increase in MAP and the accompanying bradycardia. However, the long latency pressor and cardioacceleratory responses were not altered by ganglionic blockade and adrenalectomy. Selective bilateral electrolytic or kainic acid lesions of the region of the PVH significantly attenuated the cardiovascular responses elicited by stimulation of the SFO. These data suggest that activation of neurons in the SFO elicit cardiovascular responses partially mediated by sympathetic outflow through a neural pathway involving the PVH.     

Slowing and attenuation of baroreflex heart rate control with nitrous oxide in exercising men.

The objective of the present study was to determine whether mild inert-gas narcosis impairs cardiovascular control mechanisms and contributes to the relative bradycardia that occurs in humans exercising in a hyperbaric environment. Eight healthy subjects were exposed to a normoxic 30% nitrous oxide (N(2)O) mixture and an air control during dynamic exercise of 100-W intensity. Beat-by-beat heart rate (HR) and invasive arterial blood pressure measurements were made. The sensitivity and the response latency of the arterial-cardiac-chronotropic baroreflex were determined from repeated blood pressure and HR transients induced by rapid tilts between the upright and supine posture. A significant increase (37%, P 相似文献