Vasodilator Nerves Research Articles

Hypercapnia relaxes cerebral arteries and potentiates neurally-induced relaxation.

The present study was designed to determine whether relaxations induced by hypercapnia depend upon nitric oxide (NO) derived from the endothelium, and whether NO-mediated relaxant response to electrical and chemical stimulation of vasodilator nerves is modulated by hypercapnia. In canine and monkey cerebral arterial strips contracted with K+, raising the level of CO2 of the aerating gas in the bathing media from 5 to 10% produced a moderate relaxation, together with an increased Pco2 (from 29.8 to 59.3 mm Hg) and a decreased pH (from 7.43 to 7.15). Relaxation was not influenced by endothelium denudation and treatment with NG-nitro-L-arginine. Contractions elicited by the NO synthase inhibitor were attenuated by the removal of the endothelium. Relaxations, caused by transmural electrical stimulation and nicotine, of canine cerebral arterial strips contracted with prostaglandin F2 alpha, were potentiated only slightly by hypercapnia, but the potentiation of the response to exogenous NO (acidified NaNO2) was clearly greater. It is concluded that as far as the arteries used are concerned, hypercapnia does not seem to liberate NO from the endothelium but does potentiate the effect of NO. The reason for lesser potentiation, by hypercapnia, of the response to nitroxidergic nerve stimulation than to NO action may be associated with an impairment by intracellular acidosis of NO synthase activation.

The discovery of vasomotor nerves.

The relative contribution of Claude Bernard and Charles Edouard Brown-Séquard to the discovery of vasomotor nerves is described and discussed. The controversy surrounding these two founding fathers of autonomic physiology and pharmacology is also summarized. In 1851, Bernard showed that section of the cervical sympathetic nerve unexpectedly elicited a marked and rapid increase in skin temperature. In 1852, Brown-Séquard extended these observations and established the relationship between blood vessels and the sympathetic nervous system. Thus, Brown-Séquard was the first to demonstrate the existence of sympathetic vasoconstrictor fibres. In contrast, Bernard discovered vasodilator nerves and is the founder of the modern concept of vasomotricity.

Neurogenic nitric oxide (NO) in the regulation of cerebroarterial tone

Sympathetic vasoconstrictor nerves are commonly recognized to mainly control the vascular smooth muscle tone, thus alters regional vascular resistance and blood flow. In contrast to peripheral organs and tissues, regulation by sympathetic nerves of blood flow in the brain is not so evident, and conversely vasodilator innervation is expected to play an important role. The mechanism underlying the neurogenic vasodilation in the cerebral artery has not been determined until recently. This problem was solved by the discovery of nitric oxide (NO) synthase inhibitors. Cerebral arterial dilatation caused by nerve stimulation is abolished by NO synthase inhibition and is restored by l-arginine, a substrate of NO synthase; vasodilator nerve stimulation increases the production of cyclic GMP in the tissue and liberates NO x (nitroxy compounds) from the arterial strip into superfusate. In addition, the presence of neurons containing NO synthase is histochemically demonstrated in the arterial wall. Neurogenic cerebral arterial dilation is thus hypothesized to be mediated by NO liberated as a neurotransmitter from the nerve. Nitroxidergic vasodilator innervation from the pterygopalatine ganglion would be important in the regulation of brain circulation.

Blood Substitutes

Blood Substitutes

P-325 - Effect of chronic administration of TCV-116, a novel nonpeptide angiotensin II receptor antagonist, on vasodilation mediated by calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in spontaneously hypertensive rats (SHR).

P-325 - Effect of chronic administration of TCV-116, a novel nonpeptide angiotensin II receptor antagonist, on vasodilation mediated by calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in spontaneously hypertensive rats (SHR).

Comparison of Neurogenic Contraction and Relaxation in Canine Corpus Cavernosum and Penile Artery and Vein

Functional roles of autonomic efferent nerves were compared in the isolated canine corpus cavernosum, penile artery and penile vein that participate in the penile erection by changing blood distribution. Nicotine produced moderate contraction in the arterial strips, but only a slight or no contraction in the corpus and venous strips. The contraction was suppressed or reversed to a relaxation by prazosin. Under α1-adrenoceptor blockade, relaxations induced by nicotine were in the order of the corpus > artery » vein. The response was abolished by NG-nitro-L-arginine (L-NA) and restored by L-arginine. The responses to nicotine and exogenous nitric oxide (NO) were abolished by oxyhemoglobin. The relaxant response to transmural electrical stimulation at 5 Hz was greater in the corpus than venous strips treated with prazosin, and it was abolished by L-NA. Contractions caused by nicotine under treatment with L-NA were greater in the artery than in the vein and corpus. Histochemical studies demonstrated nerve fibers containing NO synthase and tyrosine hydroxylase immunoreactivity in the corpus cavernosum, artery and vein. It is concluded that the canine corpus cavernosum, penile artery and penile vein are innervated by adrenergic, vasoconstrictor and nitroxidergic, vasodilator nerves; neurogenic vasodilatation is predominant in the corpus muscle, whereas neurogenic vasoconstriction predominates in the artery. Such a different functioning of the nerves may be responsible for the penile erection.

Actions of vasodilator nerves on arteriolar smooth muscle and neurotransmitter release from sympathetic nerves in the guinea-pig small intestine.

1. Brief constrictions of arterioles of the isolated submucosa of the guinea-pig small intestine were evoked by stimulation of the perivascular sympathetic nerves. Prior stimulation of vasodilator neurones in the submucosal nerve plexus greatly reduced the constrictor response to sympathetic stimulation. 2. Vasodilator nerve stimulation reduced both the amplitude and rate of decay of the excitatory junction potential (EJP) evoked in the arteriolar smooth muscle by sympathetic nerve stimulation. 3. Computer simulation of the effect of membrane resistance changes on the EJP amplitude indicated that the change in amplitude could not be explained by the fall in membrane resistance alone, suggesting that vasodilator nerve activity reduced neurotransmitter release from the sympathetic nerves.

Nitroxidergic nerve stimulation relaxes human uterine vein

The predominant action of nitroglycerin, a nitric oxide (NO) donor, on veins over arterioles is well recognized. This study was carried out to determine whether endogenous NO derived from vasodilator nerve regulates the tone of human uterine venous strips. The isolated vein partially contracted with prostaglandin F 2α responded to nicotine with a contraction or a relaxation; the contraction was reversed to a relaxation by prazosin, and the relaxation was potentiated by the α 1-adrenoceptor antagonist. In prazosin-treated strips, nicotine-induced relaxations were not affected by timolol, atropine and indomethacin but were abolished by oxyhemoglobin and N G-nitro- l-arginine ( l-NA), a NO synthase inhibitor. The d-enantiomer was without effect. The inhibition by l-NA was reversed by l-arginine. The NO-induced relaxation was not influenced by l-NA but was abolished by oxyhemoglobin. It may be concluded that the human uterine vein is innervated by vasodilator nerves from which NO is liberated as a vasodilator neurotransmitter. Norepinephrine from adrenergic nerves contracts venous smooth muscle possibly via stimulation of α 1-adrenoceptors.

PEPTIDES AS NEUROTRANSMITTERS IN VASCULAR AUTONOMIC NEURONS

1. Neuropeptides are present in the majority of autonomic neurons projecting to blood vessels, where they are co-localized with non-peptide transmitters and sometimes with other peptides. 2. Neuropeptides are released from vasoconstrictor and vasodilator nerve terminals after high frequency stimulation ( > 2-5Hz) with trains of impulses. 3. Neuropeptides can have potent post-synaptic effects on vascular tone, but often these effects are restricted to selected regions of the vasculature. 4. Post-synaptic effects of neuropeptides tend to be more slowly-developing and more long-lasting than those of non-peptide transmitters. 5. Autonomic vasoconstrictor and vasodilator responses often have multiple phases, with the faster phases being mediated by non-peptide transmitters and the slower phases medicated predominantly by one or more neuropeptides. 6. Some neuropeptides do not seem to have post-synaptic effects in a particular vascular bed, but can have presynaptic actions on neurotransmitter release. 7. Neuropeptides form an important component of the repertoire of neurotransmitters used by vascular autonomic neurons to regulate regional blood flow in response to a range of physiological stimuli.

Basilar arterial constriction caused by intracisternal NG-nitro-L-arginine in anesthetized monkeys

The present study was designed to determine whether tonic nitric oxide (NO)-mediated vasodilator innervation participates in basilar arterial dilatation in the anesthetized Japanese monkey. The basilar arterial diameter was angiographically measured, and NG-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, was intracisternally applied. The injection of L-NNA produced a sustained constriction of the basilar artery, the effect being reversed by the cisternal injection of L-arginine. The vasoconstriction tended to be accelerated by treatment with phentolamine. Under alpha-adrenoceptor blockade, hexamethonium significantly attenuated the vasoconstrictor response to L-NNA. Intracisternal injections of this inhibitor did not alter the systemic blood pressure and heart rate. These findings suggest that construction by the NO synthase inhibitor of the monkey basilar artery is associated with suppression of synthesis of NO in vasodilator nerves receiving tonic impulses from the central nervous system. The basilar arterial tone appears to be regulated by nitroxidergic and adrenergic nerves and by NO derived from the endothelium in anesthetized monkeys.

Neurogenic vasodilation in canine uterine and iliac arteries.

To investigate neurogenic control of uterine and iliac arterial tone with reference to nerve-derived nitric oxide. Mechanisms underlying the response to perivascular nerve stimulation were studied under alpha-adrenoceptor blockade. Mechanical responses to nerve stimulation by nicotine were isometrically recorded in isolated canine uterine and iliac arterial strips. Nitric oxide synthase was stained immunohistochemically. The arterial strips responded to nicotine mainly with a contraction, which was reversed to a relaxation by prazosin. The responses were abolished by hexamethonium. The relaxation was not influenced by timolol and atropine but was suppressed by NG-nitro-L-arginine, a nitric oxide synthase inhibitor; the inhibition was reversed by L-arginine. Internal iliac arterial strips also responded to nicotine with a relaxation under prazosin treatment, the magnitude of which was appreciably less than that in the uterine artery. Histochemical study demonstrated that perivascular nerve fibres exhibit nitric oxide synthase immunoreactivity. Canine uterine arteries are innervated by adrenergic, vasoconstrictor and nitroxidergic vasodilator nerves, and the neurogenic vasodilation is evidently more marked than that in other canine arteries, including the iliac artery.

Visceral vasodilatation and somatic vasoconstriction evoked by acid challenge of the rat gastric mucosa: diversity of mechanisms.

1. Acid back-diffusion through a disrupted gastric mucosal barrier increases blood flow to the stomach without any change in systemic blood pressure. This study was undertaken to examine the gastric acid-evoked changes in blood flow in a number of visceral and somatic arterial beds and to elucidate the mechanisms which lead to the regionally diverse haemodynamic responses. 2. The gastric mucosa of urethane-anaesthetized rats was challenged with acid by perfusing the stomach with ethanol (15%, to disrupt the gastric mucosal barrier) in 0.15 M HCl. Blood flow was estimated by laser Doppler flowmetry, the hydrogen clearance method or the ultrasonic transit time shift technique. 3. Gastric acid challenge increased blood flow in the gastric mucosa and left gastric artery while blood flow in the femoral artery and skin declined. 4. Afferent nerve stimulation by intragastric administration of capsaicin enhanced blood flow in the left gastric artery but did not diminish blood flow in the femoral artery when compared with the vehicle. 5. The gastric acid-evoked dilatation of the left gastric artery was depressed by acute extrinsic denervation of the stomach, capsaicin-induced ablation of afferent neurones or hexamethonium-induced blockade of autonomic ganglionic transmission. 6. The gastric acid-induced constriction of the femoral artery was attenuated by acute extrinsic denervation of the stomach but left unaltered by capsaicin, hexamethonium, guanethidine, indomethacin, telmisartan (an angiotensin II antagonist), [d(CH2)5(1), Tyr(Me)2, Arg8]-vasopressin (a vasopressin antagonist), bosentan (an endothelin antagonist) and acute ligation of the blood vessels to the adrenal glands. 7. These data show that acid challenge of the gastric mucosa elicits visceral vasodilatation and somatic vasoconstriction via divergent mechanisms. The gastric hyperaemia is brought about by extrinsic vasodilator nerves, whereas the reduction of somatic blood flow seems to be mediated by non-neural, probably humoral, vasoconstrictor messengers that remain to be identified.

Effects of ginsenosides on vasodilator nerve actions in the rat perfused mesentery are mediated by nitric oxide.

This study was designed to explore the effect of ginsenosides, saponins from Panax ginseng, on the vasodilator nerve actions in the rat perfused mesentery and the mechanism of this effect. In the rat perfusion mesentery, when adrenergic nerves were blocked by guanethidine (5 x 10(-6) M) and vascular muscle tone was increased with methoxamine (5 x 10(-6)-10(-5) M), transmural field stimulation produced a frequency-dependent vasodilator response, which is due to the release of calcitonin gene-related peptide; ginsenosides significantly suppressed this vasodilator response in a concentration-dependent manner (3-30 micrograms mL-1). After pretreatment with saponin (50 micrograms mL-1, 3 min) to damage endothelial cells, this suppressing effect of ginsenosides was unaltered. However, the effect was abolished by N omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M), an inhibitor of nitric oxide synthesis and addition of L-arginine (3 x 10(-4) M) restored this suppressing effect. Methylene blue (10(-5) M), an inhibitor of guanylate cyclase, also abolished the suppressing effect of ginsenosides. However, ginsenosides did not alter the relaxation responses caused by exogenous calcitonin gene-related peptide administration. We conclude that ginsenosides can produce an inhibitory effect on the vasodilator response prejunctionally in the rat perfused mesentery and that this effect of ginsenosides may be mediated by nitric oxide released from non-adrenergic, non-cholinergic nerves.

Calcitonin Gene-Related Peptide Mediates Acetylcholine-Induced Endothelium-Independent Vasodilation in Mesenteric Resistance Blood Vessels of the Rat

The role of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in acetylcholine chloride (ACh)-induced vasodilation was studied in the perfused mesenteric vascular bed isolated from the rat. Bolus infusions of ACh at smaller doses (0.1 and 1 nmol) produced rapid and short-lived vasodilation. However, larger doses (10 and 100 nmol) of ACh caused a rapid and subsequent long-lasting vasodilator response in which the duration of vasodilation was prolonged in a concentration-dependent manner. Pretreatment with capsaicin (1 mumol/L for 20 minutes) significantly shortened the duration of vasodilator response to ACh but did not affect the initial rapid phase of ACh-induced vasodilation. Chemical removal of the vascular endothelium by perfusion with sodium deoxycholate (1.75 to 1.80 mg/mL) for 30 seconds and subsequent treatment with N omega-nitro-L-arginine (100 mumol/L) to inhibit nitric oxide synthesis abolished the initial rapid vasodilator action of ACh at any given concentration. However, in the same preparation, increasing concentrations (from 1 to 1000 nmol) of ACh produced only the long-lasting vasodilator responses in a concentration-dependent manner. This long-lasting vasodilator response to ACh infusion was abolished by capsaicin pretreatment (1 mumol/L), human CGRP[8-37] (CGRP receptor antagonist, 1 mumol/L), and atropine (muscarinic ACh receptor antagonist, 1, 10, and 100 nmol/L) but not by hexamethonium (nicotinic ACh receptor antagonist, 1 and 10 mumol/L). In the preparations without endothelium, the bolus infusion of ACh (300 nmol for 30 seconds) evoked a long-lasting vasodilation and release of CGRP-like immunoreactivities into the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of vasoconstriction mediated by neuropeptide Y Y2 receptors in arterioles of the guinea‐pig small intestine

Brief applications of a high-K+ solution were used to evoke transient constrictions of arterioles from the guinea-pig small intestine. Analogues of neuropeptide Y (NPY) selective for Y2-receptors reduced the constrictions, whereas NPY or a Y1-selective analogue potentiated the constrictions. We conclude that arteriolar smooth muscle has both Y1 and Y2 receptors, and suggest that Y2 receptors inhibit vasoconstriction by modulating the opening of voltage-sensitive Ca2+ channels. This may be related to the role of NPY that is present in some vasodilator nerves.

Nitroxidergic Innervation in Dog and Monkey Renal Arteries

We analyzed mechanisms underlying neurogenic vasodilatation in dog and Japanese monkey renal arteries. Isometric mechanical responses of the arterial strip to nerve stimulation by nicotine were recorded. Nicotine-induced contractions were abolished by hexamethonium and potentiated by NG-nitro-L-arginine, a nitric oxide synthase inhibitor. The potentiating effect was reversed by L-arginine. NG-Nitro-L-arginine did not potentiate the contraction caused by norepinephrine. The nicotine-induced contraction was reversed to a relaxation by prazosin. The relaxation was not influenced by indomethacin, timolol, or atropine but was abolished by NG-nitro-L-arginine, methylene blue (a guanylate cyclase inhibitor), oxyhemoglobin (a nitric oxide scavenger), and hexamethonium. In the strips treated with NG-nitro-L-arginine, the nicotine-induced relaxation was restored by L-arginine. Histochemical study demonstrated perivascular nerves containing NADPH diaphorase and nitric oxide synthase immunoreactivity in dog and monkey arteries. We conclude that renal arteries are innervated by nitric oxide-mediated vasodilator and adrenergic vasoconstrictor nerves, and depression of the vasodilator nerve function by nitric oxide synthase inhibition potentiates the contraction caused by adrenergic nerve excitation.

Assessment of noninvasive tests of cutaneous vascular control in the forearm using a laser Doppler meter and a Finapres blood pressure monitor.

The control of human forearm cutaneous vascular resistance was examined using a combination of laser Doppler perfusion measurement and continuous Finapres blood pressure measurement. Tests which provoke changes in blood flow via different control mechanisms (local and neural) were applied in a group of ten healthy subjects. The purpose was to select from them a suitable (i.e. statistically significant) group to apply in cases where a disease process is suspected of interfering with the control of the skin circulation. Deep inspiration, immersion of the feet in water at 15 degrees C (both eliciting sympathetic vasoconstrictor nerve activity) and arm dependency (eliciting the local veni-arteriolar response) produced statistically significant, symmetrical increases in cutaneous vascular resistance in both arms (p < 0.05, Wilcoxon's test for paired differences). Similarly, post-ischaemic reactive hyperaemia (mediated by local vasodilator mechanisms) and indirect heating of the body (eliciting increased sympathetic vasodilator nerve activity) resulted in significant decreases in cutaneous vascular resistance (p < 0.01). When deep inspiration was repeated from a vasodilated baseline after indirect heating, the increases in cutaneous vascular resistance were smaller than those obtained before heating. Isometric handgrip exercise failed to produce a significant change in contralateral cutaneous vascular resistance (p > 0.05). There were no differences between right and left arms for any test (p > 0.05). The successful tests were subjected to power analysis in order to predict likely patient sample sizes required to demonstrate altered responsiveness at sites of microcirculatory disturbance compared with normal skin.

Nitroxidergic nerves and hypertension.

We studied vasodilator innervation in canine cerebral arteries and analyzed mechanisms of neurally induced vasodilatation. Available pharmacological, biochemical and histological evidence supports the hypothesis that nitric oxide (NO) synthesized in nerve terminals acts as a neurotransmitter that activates soluble guanylate cyclase in vascular smooth muscle and increases the production of cyclic GMP, resulting in relaxation. Peripheral arteries, such as the mesenteric, temporal, saphenous, uterine, and retinal, arteries, respond to nerve stimulation with contractions that are reversed to relaxations by alpha-adrenoceptor blockade. The relaxation is also mediated by NO derived from perivascular nerves. Thus, reciprocal regulation by NO-mediated (nitroxidergic) and adrenergic nerves is speculated. Potentiation by NO synthase inhibitors of the arterial contraction associated with adrenergic nerve stimulation in vitro is ascribed to depressed vasodilator nerve function. Systemic blood pressure in anesthetized dogs is increased by intravenous injections of NO synthase inhibitors. Our evidence strongly suggests that the pressor response is associated with suppressed synthesis and release of NO derived mainly from vasodilator nerves. It is concluded that nitroxidergic vasodilator nerves play important roles in the regulation of vascular tone in vitro and in vivo and in the control of systemic blood pressure. Presented here are new concepts for the mechanism of hypertension and the role played by NO-mediated nerve function.

Age-related changes in vascular responses mediated by vasoconstrictor and vasodilator nerves in SHR

Age-related changes in vascular responses mediated by vasoconstrictor and vasodilator nerves in SHR

Roles of NO and NOS-containing postganglionic vasodilator nerves in maintenance of local CBF under resting conditions in the rat

Roles of NO and NOS-containing postganglionic vasodilator nerves in maintenance of local CBF under resting conditions in the rat