Tail arteries from chronically spinalized rats have potentiated responses to nerve stimulation in vitro

Patients with severe spinal cord lesions that damage descending autonomic pathways generally have low resting arterial pressure but bladder or colon distension or unheeded injuries may elicit a life-threatening hypertensive episode. Such episodes (known as autonomic dysreflexia) are thought to result from the loss of descending baroreflex inhibition and/or plasticity within the spinal cord. However, it is not clear whether changes in the periphery contribute to the exaggerated reflex vasoconstriction. The effects of spinal transection at T7–8 on nerve- and agonist-evoked contractions of the rat tail artery were investigated in vitro . Isometric contractions of arterial segments were recorded and responses of arteries from spinalized animals ('spinalized arteries') and age-matched and sham-operated controls were compared. Two and eight weeks after transection, nerve stimulation at 0.1–10 Hz produced contractions of greater force and duration in spinalized arteries. At both stages, the α-adrenoceptor antagonists prazosin (10 n m ) and idazoxan (0.1 μ m ) produced less blockade of nerve-evoked contraction in spinalized arteries. Two weeks after transection, spinalized arteries were supersensitive to the α₁-adrenoceptor agonist phenylephrine, and the α₂-adrenoceptor agonist, clonidine, but 8 weeks after transection, spinalized arteries were supersensitive only to clonidine. Contractions of spinalized arteries elicited by 60 m m K⁺ were larger and decayed more slowly at both stages. These findings demonstrate that spinal transection markedly increases nerve-evoked contractions and this can, in part, be accounted for by increased reactivity of the vascular smooth muscle to vasoconstrictor agents. This hyper-reactivity may contribute to the genesis of autonomic dysreflexia in patients.     

Membrane properties of rabbit basilar arteries and their responses to transmural stimulation

Changes in membrane potential of rabbit basilar arteries were recorded in response to transmural stimuli applied by means of a suction electrode. Responses to current pulses of long duration and low intensity showed that the passive electrical properties of basilar arteries were similar to those of other vascular smooth muscles. In contrast to peripheral arteries, action potentials were readily evoked by depolarizing currents. Action potentials were graded in amplitude from 17–60 mV according to stimulus strength. Amplitudes and rates of rise of the directly evoked action potentials increased with increasing external calcium and were abolished by cobalt, manganese and magnesium. Brief electrical stimuli which might have been expected to activate perivascular nerves produced slow depolarizing responses whose amplitude and duration increased with increasing stimulus intensity. These responses were not blocked by tetrodoxin, lowered external calcium, or sympathetic denervation. They do not appear to be due to the release of a conventional neurotransmitter.     

Relaxant responses to transmural stimulation and nicotine of dog and monkey cerebral arteries

In helical strips of dog and monkey cerebral arteries contracted with prostaglandin F2 alpha, transmural stimulation and nicotine produced relaxations that were abolished by tetrodotoxin and hexamethonium, respectively. These responses were attenuated by quinidine, whereas relaxations of dog coronary arteries to transmural stimulation and isoproterenol were unaffected. Treatment with vasoactive intestinal polypeptide (VIP) and substance P (SP) abolished the relaxant response of cerebral arteries to repeated applications of VIP and SP, respectively; however, after VIP or SP, a normal relaxant response to transmural stimulation or nicotine was produced. Aminophylline suppressed relaxations induced by ATP but not by nerve stimulation. VIP, SP, and adenosine 5'-triphosphate (ATP) relaxed dog cerebral arteries; the responses were unaffected by quinidine. However, only VIP and ATP relaxed monkey cerebral arteries, and SP contracted the arteries. Acetylcholine contracted monkey arteries, in which transmural stimulation produced a relaxation. It may be concluded that nerves innervating the cerebrospinal wall are stimulated electrically and chemically by nicotine, resulting in the arterial relaxation. However, a vasodilator transmitter was not identified. Quinidine appears to selectively antagonize the action of the transmitters on cerebroarterial smooth muscle.     

Glucagon inhibition of hepatic arterial responses to hepatic nerve stimulation

The hepatic arterial vascular bed of the chloaralose-urethan-anesthetized dog was perfused with blood from a cannulated femoral artery. Hepatic arterial blood flow and perfusion pressure were measured. The hepatic periarterial postganglionic sympathetic nerves were stimulated supramaximally at 0.1, 0.5, 1, 2, 5, 10, and 20 Hz; this caused frequency-dependent rises in the calculated hepatic arterial vascular resistance at all frequencies above the threshold of 0.1 or 0.5 Hz. Glucagon was infused intra-arterially in dosese from 0.25 to 10 microgram/min; glucagon antagonized both the vasoconstrictor effects of hepatic nerve stimulation and of intra-arterial injections of norepinephrine. The degree of antagonism of these responses was significantly correlated with the calculated hepatic arterial glucagon concentration. It is possible that glucagon released physiologically in stress and hypoglycemia may protect the hepatic arterial vasculature from the effects of increased sympathetic discharge.     

Cardiovascular responses to electrocardiogram-coupled stimulation of rabbit aortic nerve.

Electrical stimulation of the rabbit's aortic nerve during one or more cardiac cycles resulted in a reflex fall in heart rate and mean arterial blood pressure (MAP). The onset of bradycardia and of fall in MAP were independent of the number of beats stimulated. The initial slope of the heart rate and MAP responses increased as the number of beats stimulated increased, reaching a maximum at five beats of stimulation. Bradycardia peaked 8 and 10 beats after the end of one and two cycles of stimulation, respectively, while the peak response occurred at, or prior to, the end of stimulation when 12 or more beats were involved. Onset and recovery of both responses were consistent, and seldom did MAP indicate a return toward control during stimulation. Thus, central nervous system modulation of sympathetic activity to the peripheral vasculature was sustained as long as the aortic nerve input was maintained. However, reflex control of heart rate was more complex, involving simultaneous alteration in both vagal and sympathetic efferent activity.     

Thermal and mechanical responses of the amphibian skin to nerve stimulation.

The isolated calf skin of the toad and bullfrog was found to generate a burst of heat in response to stimulation of the cutaneous nerve. The electric responses of the skin evoked by nerve stimulation invariably lagged behind the heat burst. The generation of a heat burst was followed by a slow mechanical response of the skin. Suppression of these responses by adrenergic blocking agents suggests that heat is produced at the junction between the gland cells and the sympathetic nerve fibers. Large mechanical changes in the skin were observed when noradrenaline was applied to the inner surface of the skin.     

Factorial analysis of the cardiovascular responses to carotid sinus nerve stimulation

The changes in arterial blood pressure, heart period, and respiration evoked by carotid sinus nerve (CSN) stimulation were studied in closed-chest, anesthetized dogs. Multifactorial regression equations were derived to express the various steady-state responses as functions of the parameters of stimulation. With the CSN and vagi intact, the changes in arterial pressure produced by CSN stimulation were much less pronounced than after the CSN and vagi were interrupted. When the CSN and vagi were intact, changes in stimulus duration had relatively little influence on heart period at the lower voltage levels. However, at higher voltages, increases in pulse duration produced substantial increments in heart period. TheRR interval increased progressively as the frequency of CSN stimulation was varied from 15 to 45 Hz; the magnitude of this effect varied directly with the stimulus voltage. This work was supported by U.S. Public Health Service Grants HL 15758 and HL 10951 from the National Heart and Lung Institute.     

Arousal responses to olfactory or trigeminal stimulation during sleep

STUDY OBJECTIVES: The interaction of sensory physiology and sleep has been studied for various sensory systems. Nevertheless, the question whether chemosensory (especially olfactory) stimuli may lead to arousals during sleep remains under discussion. Specifically, the central processing of olfactory information shows fundamental differences compared to other sensory systems. DESIGN: Prospective controlled trial. SETTING: Sleep research facility, University Hospital. PARTICIPANTS: Five young healthy, normosmic volunteers. INTERVENTION: Intranasal chemosensory stimulation during sleep was based on air-dilution olfactometry. For olfactory stimulation H2S (smell of rotten eggs) was used in 4 concentrations (1, 2, 4, and 8 ppm). For trigeminal stimulation CO2 (stinging sensation) was also administered in 4 concentrations (10%, 20%, 40%, and 60% v/v) while odorless stimuli were used for control. MEASUREMENTS: Arousal reactions due to chemosensory stimulation were assessed during overnight polysomnography 30 seconds after the presentation of every stimulus during 23 nights of testing. RESULTS: For olfactory testing, an average number of 703 olfactory stimuli and 157 odorless controls were used for analysis per subject. Even the highest stimulus concentration did not produce an increase in arousal frequency. For trigeminal testing, an average number of 405 stimuli and 79 controls were used for analysis per subject, and an increase in arousal frequency was observed following the increase of stimulus concentration. CONCLUSIONS: With the present results we were able to demonstrate that, in contrast to trigeminal stimulation, the presentation of a strong but selective olfactory stimulus does not lead to arousals during nocturnal sleep in humans.     

Cardiac vagal and sympathetic nerve responses to baroreceptor stimulation in the dog

The effects of ascending stepwise pressure changes in the isolated carotid sinuses on cardiac vagal and sympathetic nerve activities were studied in anesthetized, open chest dogs. The steady state responses of the cardiac vagal and the sympathetic nerve activity and arterial blood pressure were plotted against the sinus pressure and the relations were approximated by the normal distribution function (response curve). The sinus pressure- vs. reflex gain relations (reflex gain curve) were approximated by the normal density function. The maximum gain and the range of change were found to be greater for the vagal than for the sympathetic and arterial pressure responses. The sinus pressure values derived from response curves and reflex gain curves for vagal and sympathetic nerve responses were close to each other, while these values and those obtained from arterial pressure responses were considerably apart. It was concluded that: (1) The cardiac vagal neurons are more sensitive to the baroreceptor input than the sympathetic neurons; (2) The similar type of baroreceptor afferent inputs reach the cardiac vagal and the sympathetic structures which are controlling the autonomic outflows.     

Postnatal development of inotropic responses to nerve stimulation and tyramine in rat atria

Summary Inotropic responses were measured in isolated rat left atria using an isometric force transducer. In atria from adult rats tyramine administration or field stimulation of intramural cardiac nerves (in the presence of atropine) caused a positive inotropic response which was as great as that obtainable with exogenous noradrenaline. In contrast, atria from newborn animals showed very poor inotropic responses to nerve stimulation or tyramine although they already responded well to noradrenaline. The responses developed progressively with age, reaching adult levels at 3 to 4 weeks of age. It is concluded that the postnatal development of myocardial sympathetic nerves is correlated with a development of the positive inotropic response to sympathetic nerve stimulation or to tyramine.     

Constrictor response of small pulmonary arteries to acute pulmonary hypertension during left atrial pressure elevation

Acute elevations in left atrial pressure (LAP) were induced by altering the volume of air within a balloon inserted into the left atrium; the changes in internal diameter (ID) of small muscular pulmonary arteries (100-600 microns ID) in response to the associated rises of pulmonary arterial pressure (PAP) were measured using an X-ray TV system on the in vivo cat lung. When LAP was elevated to 14 +/- 1, 24 +/- 1, and 30 +/- 1 mmHg, PAP was increased to 21 +/- 1, 30 +/- 1, and 37 +/- 1 mmHg, respectively. With PAP ranging from 16 (control value) to 21 mmHg the ID did not dilate significantly. With PAP of 30-37 mmHg significant ID dilation occurred. The magnitude of the ID dilation (16%) with PAP of 37 mmHg, however, was significantly smaller than that (20%) with PAP of 30 mmHg despite the greater pressure rise. When the elevated PAP of 30-37 mmHg was quickly returned to the control level by rapid balloon deflation, the ID constricted significantly below the control level. The magnitude of the ID constriction was proportional to the degree of the preceding PAP rise and was maximal in the arteries of 200-400 microns ID. A papaverine hydrochloride injection combined with the balloon deflation completely abolished the ID constriction. A phentolamine injection, on the other hand, significantly attenuated the constriction with approximately half of the constriction persisting. The results indicate that an increase in vascular smooth muscle tone occurred in the small muscular pulmonary arteries, particularly those of 200-400 microns ID, in response to the acute rise of PAP above 30 mmHg during the LAP elevation. In addition, the data suggest the partial participation of catecholamines in the active contraction of vascular smooth muscle. The arterial contraction may serve to protect the pulmonary capillaries from an excessive hydrostatic pressure and pulmonary edema.