Parasympathetic reflex vasodilation in the cerebral hemodynamics of rats

We investigated the role of parasympathetic reflex vasodilation in the regulation of the cerebral hemodynamics, and whether GABA_A receptors modulate the response. We examined the effects of activation of the parasympathetic fibers through trigeminal afferent inputs on blood flow in the internal carotid artery (ICABF) and the cerebral blood vessels (rCBF) in parietal cortex in urethane-anesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited intensity- and frequency-dependent increases in ICABF that were independent of changes in external carotid artery blood flow. Increases in ICABF were elicited by LN stimulation regardless of the presence or absence of sympathetic innervation. The ICABF increases evoked by LN stimulation were almost abolished by the intravenous administration of hexamethonium (10 mg kg^?1) and were reduced significantly by atropine administration (0.1 mg kg^?1). Although the LN stimulation alone had no significant effect on rCBF, LN stimulation in combination with a blocker of the GABA_A receptor pentylenetetrazole increased the rCBF markedly. This increase in rCBF was reduced significantly by the administration of hexamethonium and atropine. These observations indicate that the increases in both ICABF and rCBF are evoked by parasympathetic activation via the trigeminal-mediated reflex. The rCBF increase evoked by LN stimulation is thought to be limited by the GABA_A receptors in the central nervous system. These results suggest that the parasympathetic reflex vasodilation and its modulation mediated by GABA receptors within synaptic transmission in the brainstem are involved in the regulation of the cerebral hemodynamics during trigeminal afferent inputs.     

Occurrence of parasympathetic vasodilator fibers in the lower lip of the guinea-pig

The present study was designed to examine whether there are parasympathetic vasodilator fibers in the lower lip of the guinea-pig. Electrical stimulation of the central cut end of the lingual nerve of guinea-pigs evoked intensity- and frequency-dependent decreases in lower lip blood flow and systemic arterial blood pressure (SABP). Pretreatment with guanethidine, a postganglionic sympathetic nerve blocker and antihypertensive drug (30 mg kg⁻¹, s.c., 24 h prior to experiments), reduced the magnitude of the decrease in SABP while the intensity- and frequency-dependent increases of the lip blood flow occurred by the lingual nerve stimulation only on the side ipsilateral to stimulation. Increases in the lip blood flow evoked by lingual nerve stimulation in guanethidine pretreated guinea-pigs were reduced by hexamethonium (an autonomic ganglion cholinergic blocker) in a dose-dependent manner. When fluoro-gold (a retrograde neural tracer) was injected into the lower lip, labeled neurons were observed in the ipsilateral otic ganglion. The present study indicates the presence of parasympathetic vasodilator fibers originating from the otic parasympathetic ganglion in the guinea-pig lower lip, similar to those reported previously in rats, cats, rabbits and humans.     

Inhibitory effects of excess sympathetic activity on parasympathetic vasodilation in the rat masseter muscle

The present study was designed to examine the effect of sympathetic tonic activity on parasympathetic vasodilation evoked by the trigeminal-mediated reflex in the masseter muscle in urethane-anesthetized rats. Sectioning of the superior cervical sympathetic trunk (CST) ipsilaterally increased the basal level of blood flow in the masseter muscle (MBF). Electrical stimulation of the peripheral cut end of the CST for 2 min using 2-ms pulses ipsilaterally decreased in a dependent manner the intensity (0.5-10 V) and frequency (0.1-5 Hz) of the MBF. The CST stimulation for 2 min at <0.5 Hz with 5 V using 2-ms pulses seems to be comparable with the spontaneous activity in the CST fibers innervating the masseter vasculature, because this stimulation restored the basal level of the MBF to the presectioned values. Parasympathetic vasodilation evoked by electrical stimulation of the central cut end of the lingual nerve in the masseter muscle was markedly reduced by CST stimulation for 2 min with 5 V using 2-ms pulses in a frequency-dependent manner (0.5-5 Hz). Intravenous administration of phentolamine significantly reduced the vasoconstriction induced by CST stimulation in a dose-dependent manner (0.1-1 mg/kg), but pretreatment with either phentolamine or propranolol failed to affect the sympathetic inhibition of the parasympathetic vasodilation. Our results suggest that 1) excess sympathetic activity inhibits parasympathetic vasodilation in the masseter muscle, and 2) alpha- and beta-adrenoceptors do not contribute to sympathetic inhibition of parasympathetic vasodilation, and thus some other types of receptors must be involved in this response.     

GABAB receptors in the NTS mediate the inhibitory effect of trigeminal nociceptive inputs on parasympathetic reflex vasodilation in the rat masseter muscle

The present study was designed to examine whether trigeminal nociceptive inputs are involved in the modulation of parasympathetic reflex vasodilation in the jaw muscles. This was accomplished by investigating the effects of noxious stimulation to the orofacial area with capsaicin, and by microinjecting GABA(A) and GABA(B) receptor agonists or antagonists into the nucleus of the solitary tract (NTS), on masseter hemodynamics in urethane-anesthetized rats. Electrical stimulation of the central cut end of the cervical vagus nerve (cVN) in sympathectomized animals bilaterally increased blood flow in the masseter muscle (MBF). Increases in MBF evoked by cVN stimulation were markedly reduced following injection of capsaicin into the anterior tongue in the distribution of the lingual nerve or lower lip, but not when injected into the skin of the dorsum of the foot. Intravenous administration of either phentolamine or propranolol had no effect on the inhibitory effects of capsaicin injection on the increases of MBF evoked by cVN stimulation, which were largely abolished by microinjecting the GABA(B) receptor agonist baclofen into the NTS. Microinjection of the GABA(B) receptor antagonist CGP-35348 into the NTS markedly attenuated the capsaicin-induced inhibition of MBF increase evoked by cVN stimulation, while microinjection of the GABA(A) receptor antagonist bicuculline did not. Our results indicate that trigeminal nociceptive inputs inhibit vagal-parasympathetic reflex vasodilation in the masseter muscle and suggest that the activation of GABA(B) rather than GABA(A) receptors underlies the observed inhibition in the NTS.     

Parasympathetic reflex vasodilatation in rat submandibular gland

The present study was designed to investigate 1) whether parasympathetic reflex vasodilatation occurs in the submandibular gland (SMG) in deeply urethan-anesthetized, cervically vagotomized, and sympathectomized rats when the central cut end of the lingual nerve (LN) is electrically stimulated and 2) to what extent the neural mechanisms underlying such responses are the same as those involved in the response to direct stimulation of the chorda-LN (CLN). Stimulation of each nerve separately elicited a marked blood flow increase in SMG. Section of the chorda tympani abolished the SMG blood flow response but had no effect on the lip blood flow increase evoked by LN stimulation. Section of the CLN abolished the SMG blood flow increases evoked by stimulation of either nerve. The SMG blood flow increases (regardless of whether they were evoked by LN or CLN stimulation) were markedly reduced by the autonomic cholinergic ganglion blocker hexamethonium. The present study demonstrates that a parasympathetic reflex vasodilator mechanism is present in the rat SMG and that it can express its effects under deep general anesthesia.     

Absence of nonadrenergic noncholinergic relaxation in the cat cervical trachea

Published in vivo experiments have not supported in vitro reports of the presence of nonadrenergic noncholinergic (NANC) inhibitory pathways in the cat trachea. We therefore examined these pathways, measuring tension in an innervated tracheal segment, flow resistance in more distal airways, and dynamic compliance, in 10 anesthetized mechanically ventilated cats. Initially, cervical vagal stimulation evoked contraction followed by relaxation of smooth muscle of trachea and lower airways; sympathetic stimulation evoked relaxation only. After muscarinic blockade and restoration of smooth muscle tone with 5-hydroxytryptamine (5-HT) applied topically to the tracheal mucosa, vagal stimulation did not affect tracheal segment tension, whereas sympathetic-evoked relaxation was preserved. Similar results were found when tone was restored with intravenous 5-HT, with vagal stimulation also decreasing resistance and increasing compliance. We conclude that NANC pathways are present in lower airways but not in the cervical trachea of the cat. We hypothesize that parasympathetic constriction of cat airway smooth muscle can occur without simultaneous NANC activation, whereas NANC activity occurs only in tandem with parasympathetic stimulation.     

Changes in the electrical activity of the rabbit proximal colon in vivo by stimulation of the vagus and splanchnic nerves]

1. Using extracellular electrodes placed on the serosa, we recorded the modifications of the electrical activity of the colonic muslce fibers caused by the stimulation of vagal and splanchnic nerve fibers. 2. Vagal stimulation produces two types of junction potentials: excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs). The IJPs are elicited by stimulation of vagal fibers which innervate intramural non-adrenergic inhibitory neurons. 3. The conduction velocity of the nerve impulse along the vagal pre-ganglionic fibers is 1.01 m/sec for excitatory fibers and 0.5. m/sec for inhibitory fibers. 4. Splanchnic fiber stimulation causes EJP disappearance, blocking transmission between preganglionic fibers and intramural excitatory neurons, and a decrease in IJP amplitude that most likely indicates a previous hyperpolarization of the smooth muscle. 5. IJP persistence during splanchnic stimulation proves that sympathetic inhibition does not modify the transmission of the vagal influx onto the non-adrenergic inhibitory neurons of the intramural plexuses. 6. Through a comparative study of proximal and distal colonic innervation, we are able to show that there is a similar organization of both regions, that is a double inhibitory innervation: an adrenergic one of a sympathetic origin, and a non adrenergic one of a parasympathetic origin.     

The influence of L-NG-nitro-arginine on field stimulation induced contractions and acetylcholine release in guinea pig isolated tracheal smooth muscle

The interaction between parasympathetic and inhibitory non-adrenergic, non-cholinergic nerves in tracheal smooth muscle was investigated by determining the effects of the NO-synthase inhibitor L-NG-nitro-arginine (L-NOARG) on contractions and the associated acetylcholine release elicited by field stimulation of the muscle. At frequencies above 2Hz contractile responses to field stimulation were potentiated by L-NOARG (50 microM). alpha-chymotrypsin pre-treatment potentiated contractile responses at all frequencies, but the effects of L-NOARG were unaltered. The effect of L-NOARG on responses to 5Hz electrical stimulation was not mimicked by D-NOARG, was reversed by L-, but not D-arginine and was unaffected by epithelium removal. L-NOARG did not affect responses to exogenous acetylcholine nor the overflow of 3H from tissues previously loaded with [3H]-choline. It is therefore concluded that field stimulation of tracheal smooth muscle induces the release of an endogenous nitrate, which, by an inhibitory action on smooth muscle, functionally antagonises the concomitantly released parasympathetic neurotransmitter.     

VIP and noncholinergic vasodilatation in rabbit submandibular gland

The effect of parasympathetic nerve activation on rabbit submandibular gland (SMG) blood flow and saliva secretion were studied before and after systemic administration of atropine or hexamethonium. The parasympathetic fibers were stimulated electrically (2 and 15 Hz, 10 V, 1 msec) at the plexus around the submandibular salivary duct or at the chorda lingual nerve. In untreated animals, stimulation of parasympathetic fibers caused a frequency-dependent increase of salivary secretion and blood flow in the SMG. Atropine treatment completely abolished saliva secretion at 2 Hz and 15 Hz and the increase in SMG blood flow during stimulation at 2 Hz. Although atropine significantly reduced the vasodilatory response at 15 Hz, the highest blood flow measured under such circumstances was still about 2.5 times the prestimulation value. After hexamethonium administration no blood flow increase or saliva secretion was seen upon chorda lingual stimulation. The concentration of vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the venous effluent of the SMG increased during nerve stimulation. Atropine significantly reduced, and hexamethonium abolished this VIP-output elicited by parasympathetic nerve stimulation. Local infusion of VIP, peptide histidine isoleucine (PHI) and substance P all caused atropine-resistant vasodilation but no salivation. The present data suggest that VIP and possibly PHI play a role in the atropine-resistant vasodilatation in rabbit submandibular gland elicited by parasympathetic nerve stimulation. The contribution of sensory mediators such as substance P released by stimulation of afferent nerves in the chorda lingual nerve to the salivary and vasodilatory responses seems to be of minor importance in the rabbit submandibular gland.     

Effects of synthetic leukotriene D-4 on the local regulation of blood flow in human subcutaneous tissue

Prostaglandin E-1 and E-2 acts as vasodilators partly through inhibition of sympathetic nerves and partly through a direct action on smooth muscle. To elucidate the mechanisms of LTD-4 induced vasodilation, the vascular smooth muscle dependent auto-regulation of blood flow and the sympathetic reflex mechanism of the "vasoconstrictor reflex" was investigated in humans. Blood flow was measured in subcutaneous tissue after injection of 133-Xenon 1) alone, 2) mixed with lidocaine 20 mg/ml for sympathetic blockade, 3) mixed with PGE-2 0.1 ug/ml and 4) mixed with LTD-4 in concentrations of 5 and 20 microM. Blood flow was kept constant during elevation by 20 cm above heart level (preserved autoregulation) except after injection of PGE-2 and LTD-4 20 microM where a significant decrease was observed (defective smooth muscle function). During lowering by 45 cm, a decrease in blood flow by 50% was observed in experiment 1. This response was blocked by lidocaine and PGE-2, partially blocked by LTD-4 20 microM but unaffected by LTD 5 microM. LTD-4 affects vascular smooth muscle function but does not affect sympathetic reflexes in concentrations which does not have a direct smooth muscle action.     

Regional regulation of choroidal blood flow by autonomic innervation in the rat

Regional influences of parasympathetic and sympathetic innervation on choroidal blood flow were investigated in anesthetized rats. Parasympathetic pterygopalatine neurons were activated by electrically stimulating the superior salivatory nucleus, whereas sympathetic neurons were activated by cervical sympathetic trunk stimulation and uveal blood flow was measured by laser Doppler flowmetry. Parasympathetic stimulation increased flux in the anterior choroid and nasal vortex veins but not in the posterior choroid. Vasodilation was blocked completely by the neuronal nitric oxide synthase inhibitor 1-(2-trifluoromethylphenyl)imidazole but was unaffected by atropine. Sympathetic stimulation decreased flux in all regions, and this was blocked by prazosin. Parasympathetic stimulation did not affect vasoconstrictor responses to sympathetic stimulation in the posterior choroid but attenuated the decrease in blood flow through the anterior choroid and vortex veins via a nitrergic mechanism. We conclude that sympathetic alpha-noradrenergic vasoconstriction occurs throughout the choroid, whereas parasympathetic nitrergic vasodilation plays a selective role in modulating blood flow in anterior tissues of the eye.     

Does autonomic blockade reveal a potent contribution of nitric oxide to locomotion-induced vasodilation?

We sought to test the role of nitric oxide (NO) in governing skeletal muscle (iliac) vascular conductance during treadmill locomotion in dogs (n = 6; 3.2 and 6.4 km/h at 0% grade, and 6.4 km/h at 10% grade). As seen previously, the increase in muscle vascular conductance accompanying treadmill locomotion was little influenced by NO synthase inhibition alone with N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv), but the absolute value of conductance achieved during locomotion was reduced. Such ambiguous results provide an unclear picture regarding the importance of NO during locomotion. However, muscle vasodilation is normally restrained by the sympathetic system during locomotion. Thus a significant contribution by NO to the increase in vascular conductance that accompanies locomotion could be masked by partial withdrawal of the competing influence of sympathetic vasoconstrictor nerve activity secondary to the rise in arterial pressure following systemic L-NAME administration. To test this possibility, we compared the rise in muscle vascular conductance before and after L-NAME treatment while ganglionic transmission was blocked by hexamethonium. Under these conditions, L-NAME significantly reduced both the rise in vascular conductance (by 32%, P < 0.001) and the absolute level of vascular conductance (by 30%, P < 0.001) achieved during locomotion with no effect on blood flow. Thus augmented NO production normally provides a significant drive to relax vascular smooth muscle in active skeletal muscle during locomotion. Potential deficits stemming from the absence of NO following L-NAME treatment are masked by less intense sympathetic restraint when autonomic function is intact.     

Neural and humoral control of regional vascular beds via A1 adenosine receptors located in the nucleus tractus solitarii

Our previous studies showed that stimulation of adenosine A(1) receptors located in the nucleus of the solitary tract (NTS) exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and β-adrenergic vasodilation vs. sympathetic and vasopressinergic vasoconstriction. Because NTS A(1) adenosine receptors inhibit baroreflex transmission in the NTS and contribute to the pressor component of the HDR, we hypothesized that these receptors also contribute to the redistribution of blood from the visceral to the muscle vasculature via prevailing sympathetic and vasopressinergic vasoconstriction in the visceral (renal and mesenteric) vascular beds and prevailing β-adrenergic vasodilation in the somatic (iliac) vasculature. To test this hypothesis, we compared the A(1) adenosine-receptor-mediated effects of each vasoactive factor triggered by NTS A(1) adenosine receptor stimulation [N(6)-cyclopentyladenosine (CPA), 330 pmol in 50 nl] on the regional vascular responses in urethane/chloralose-anesthetized rats. The single-factor effects were separated using adrenalectomy, β-adrenergic blockade, V(1) vasopressin receptor blockade, and sinoaortic denervation. In intact animals, initial vasodilation was followed by large, sustained vasoconstriction with smaller responses observed in renal vs. mesenteric and iliac vascular beds. The initial β-adrenergic vasodilation prevailed in the iliac vs. mesenteric and renal vasculature. The large and sustained vasopressinergic vasoconstriction was similar in all vascular beds. Small sympathetic vasoconstriction was observed only in the iliac vasculature in this setting. We conclude that, although A(1) adenosine-receptor-mediated β-adrenergic vasodilation may contribute to the redistribution of blood from the visceral to the muscle vasculature, this effect is overridden by sympathetic and vasopressinergic vasoconstriction.     

Inhibition by nifedipine of the indirectly induced contractile response of the rat diaphragm

The effects of nifedipine (30 micrograms/ml) on isometric force production of in-vitro rat diaphragm were studied during direct and indirect modes of muscle activation. During direct muscle stimulation, nifedipine potentiated isometric force during twitch and unfused tetanic stimulation. Indirectly elicited responses, evoked by stimulation of the phrenic nerve, were uniformly depressed following nifedipine. Inhibition of indirect force production increased with time, while force potentiation with direct activation remained constant. We conclude that inhibitory effects of nifedipine on the phrenic nerve-diaphragm preparation are specific for nerve or neuromuscular junction.     

Reduced Blood Pressure of CFTR-F508del Carriers Correlates with Diminished Arterial Reactivity Rather than Circulating Blood Volume in Mice

The F508del mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) is the most common cause of cystic fibrosis (CF). Both CF patients and F508del carriers have decreased blood pressure. While this has been attributed to salt depletion, recent studies have shown F508del expression interferes with smooth muscle cell calcium mobilization. We tested the hypothesis that carriers of the F508del mutation have lower adult blood pressures and reduced aortic contractility without a reduction in circulating blood volume. By radiotelemetry, F508del heterozygous mice had significantly lower arterial pressures than wild-type C57BL/6 controls, with the greatest effect seen at the time of dark-to-light cycle transition (mean difference of 10 mmHg). To replicate the vascular effects of sympathetic arousal, isoproterenol and epinephrine were co-infused, and F508del mice again had significantly reduced arterial pressures. Aortas isolated from F508del heterozygous mice had significantly decreased constriction to noradrenaline (0.9±0.2 versus 2.9±0.7 mN). Inhibition of wild-type CFTR or the inositol triphosphate receptor replicated the phenotype of F508del aortas. CFTR carrier status did not alter circulating blood volume. We conclude the CFTR-F508del mutation decreases aortic contractility and lowers arterial pressures. As a cAMP-activated chloride channel that facilitates calcium mobilization, we speculate wild-type CFTR co-activation during adrenergic receptor stimulation buffers the vasodilatory response to catecholamines, and loss of this compensatory vasoconstrictor tone may contribute to the lower arterial pressures seen in heterozygote carriers of a CFTR-F508del mutation.     

Role of potassium in regulating blood flow and blood pressure

Unlike sodium, potassium is vasoactive; for example, when infused into the arterial supply of a vascular bed, blood flow increases. The vasodilation results from hyperpolarization of the vascular smooth muscle cell subsequent to potassium stimulation by the ion of the electrogenic Na+-K+ pump and/or activating the inwardly rectifying Kir channels. In the case of skeletal muscle and brain, the increased flow sustains the augmented metabolic needs of the tissues. Potassium ions are also released by the endothelial cells in response to neurohumoral mediators and physical forces (such as shear stress) and contribute to the endothelium-dependent relaxations, being a component of endothelium-derived hyperpolarization factor-mediated responses. Dietary supplementation of potassium can lower blood pressure in normal and some hypertensive patients. Again, in contrast to NaCl restriction, the response to potassium supplementation is slow to appear, taking approximately 4 wk. Such supplementation reduces the need for antihypertensive medication. "Salt-sensitive" hypertension responds particularly well, perhaps, in part, because supplementation with potassium increases the urinary excretion of sodium chloride. Potassium supplementation may even reduce organ system complications (e.g., stroke).     

Sympathetic activation increases basilar arterial blood flow in normotensive but not hypertensive rats

The close apposition between sympathetic and parasympathetic nerve terminals in the adventitia of cerebral arteries provides morphological evidence that sympathetic nerve activation causes parasympathetic nitrergic vasodilation via a sympathetic-parasympathetic interaction mechanism. The decreased parasympathetic nerve terminals in basilar arteries (BA) of spontaneously hypertensive rat (SHR) and renovascular hypertensive rats (RHR) compared with Wistar-Kyoto rats (WKY), therefore, would diminish this axo-axonal interaction-mediated neurogenic vasodilation in hypertension. Increased basilar arterial blood flow (BABF) via axo-axonal interaction during sympathetic activation was, therefore, examined in anesthetized rats by laser-Doppler flowmetry. Electrical stimulation (ES) of sympathetic nerves originating in superior cervical ganglion (SCG) and topical nicotine (10-30 μM) onto BA of WKY significantly increased BABF. Both increases were inhibited by tetrodotoxin, 7-nitroindazole (neuronal nitric oxide synthase inhibitor), and ICI-118,551 (β(2)-adrenoceptor antagonist), but not by atenolol (β(1)-adrenoceptor antagonist). Topical norepinephrine onto BA also increased BABF, which was abolished by atenolol combined with 7-nitroindazole or ICI-118,551. Similar results were found in prehypertensive SHR. However, in adult SHR and RHR, ES of sympathetic nerves or topical nicotine caused minimum or no increase of BABF. It is concluded that excitation of sympathetic nerves to BA in WKY causes parasympathetic nitrergic vasodilation with increased BABF. This finding indicates an endowed functional neurogenic mechanism for increasing the BABF or brain stem blood flow in coping with increased local sympathetic activities in acutely stressful situations such as the "fight-or-flight response." This increased blood flow in defensive mechanism diminishes in genetic and nongenetic hypertensive rats due most likely to decreased parasympathetic nitrergic nerve terminals.     

Rostral Ventrolateral Medulla: An Integrative Site for Muscle Vasodilation During Defense-Alerting Reactions

1. Evidence gathered over the last 30 years has firmly established that the rostral ventrolateral medulla (RVLM) is a major vasomotor center in the brainstem, harboring sympathetic premotor neurons responsible for generating and maintaining basal vasomotor tone and resting levels of arterial blood pressure. Although the RVLM has been almost exclusively classified as a vasopressor area, in this report we review some evidence suggesting a prominent role of the RVLM in muscle vasodilation during defense-alerting responses.2. Defense-alerting reactions are a broad class of behavior including flexion of a limb, fight/flight responses, apologies, etc. They comprise species-distinctive motor and neurovegetative adjustments. Cardiovascular responses include hypertension, tachycardia, visceral vasoconstriction, and muscle vasodilation. Since defense-alerting reactions generally involve intense motor activation, muscle vasodilation is regarded as a key feature of these responses.3. In anesthetized or unanesthetized-decerebrate animals, natural or electrical stimulation of cutaneous and muscle afferents produced hypertension, tachycardia, and vasodilation restricted to the stimulated limb.4. Unilateral inactivation of the RVLM contralateral to the stimulated limb abolished cardiovascular adjustments to stimulation of cutaneous and muscle afferents. Within the RVLM glutamatergic synapses mediate pressor responses, whereas GABAergic synapses mediates muscle vasodilation.5. In urethane-anesthetized rats, electrical stimulation of the hypothalamus elicited hypertension, tachycardia, visceral vasoconstriction, and hindlimb vasodilation. The hindlimb vasodilation induced by hypothalamic stimulation is a complex response, involving reduction of sympathetic vasoconstrictor tone, release of catecholamines by the adrenal medulla, and a still unknown system that may use nitric oxide as a mediator.6. Blockade of glutamatergic transmission within the RVLM selectively blocks muscle vasodilation induced by hypothalamic stimulation.7. The results obtained suggest that, besides its role in the generation and maintenance of the sympathetic vasoconstrictor drive, the RVLM is also critical for vasodilatory responses during defense reactions. The RVLM may contain several, distinctive mechanisms for muscle vasodilation. Anatomical and functional characterization of these pathways may represent a breakthrough in our understanding of cardiovascular control in normal and/or pathological conditions.     

Parasympathetic control of coronary blood flow

Active parasympathetic coronary vasodilation in excess of any changes in myocardial metabolism has been observed in a number of circumstances. Electrical stimulation of the cardiac end of the cut vagus nerve produces a cholinergic coronary vasodilation that is blocked by atropine. Activation of carotid body chemoreceptors, carotid sinus baroreceptors, or left ventricular receptors elicits reflex parasympathetic coronary vasodilation. The coronary vasodilation produced by these reflexes can be prevented by vagotomy or atropine. The relative importance of parasympathetic coronary control in relation to sympathetic and local metabolic coronary control awaits further research.