Effects of nifedipine on hepatic blood volume in cats: indirect venoconstriction and absence of inhibition of postsynaptic α2-adrenoceptor responses

1986 ◽  
Vol 64 (5) ◽  
pp. 615-620 ◽  
Author(s):  
R. Segstro ◽  
K. L. Seaman ◽  
I. R. Innes ◽  
C. V. Greenway
Keyword(s):  
Cardiac Output ◽  
Blood Volume ◽  
Intravenous Administration ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Adrenal Glands ◽  
Sympathetic Nerves ◽  
Direct Effects ◽  
Sympathetic Nerve Stimulation ◽  
Α2 Adrenoceptor

Intravenous administration of hypotensive doses (30–200 μg/kg) of nifedipine to cats anesthetized with pentobarbital caused an increase in cardiac output accompanied by hepatic venoconstriction. The hepatic venoconstriction and the increase in cardiac output were abolished in animals in which the hepatic sympathetic nerves were cut, the adrenal glands were excluded, and the kidneys were removed. This contrasts with the indirect hepatic venoconstrictor action of isoproterenol which was shown previously not to be abolished by these procedures. Further experiments showed that the hepatic venoconstrictor effect of nifedipine was blocked by removal of the kidneys, but not by removal of the hepatic sympathetic nerves and adrenals. These results support the hypothesis that venoconstriction plays an important role when drugs produce increased cardiac output. In nephrectomized animals, nifedipine had no direct effects on hepatic blood volume and it did not alter the effects of infusions of norepinephrine on hepatic blood volume, which have previously been shown to be mediated through α2-adrenoceptors. However, it did reduce the hepatic venous responses to hepatic sympathetic nerve stimulation by 30%.

Antagonism of vasoconstriction by muscle contraction differs with alpha-adrenergic subtype

1993 ◽  
Vol 264 (3) ◽  
pp. H892-H900 ◽  
Author(s):  
L. R. Dodd ◽  
P. C. Johnson
Keyword(s):  
Muscle Contraction ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Sympathetic Nerves ◽  
Second Order ◽  
Sartorius Muscle ◽  
Receptor Subtypes ◽  
Sympathetic Nerve Stimulation ◽  
Adrenergic Antagonist ◽  
Prejunctional Inhibition

It has been suggested that muscle contraction causes prejunctional inhibition of transmitter release from sympathetic nerves. In accordance with this, we found that second-order (50 microns ID) arterioles of the cat sartorius muscle dilate 40-80% more with muscle contraction during 2-, 4-, or 8-Hz sympathetic nerve stimulation than during equivalent constriction produced by intravenous norepinephrine injection. However, when constriction was to the selective alpha 1-agonist phenylephrine, the magnitude of dilation induced by muscle contraction was similar to that seen with sympathetic nerve stimulation, suggesting that prejunctional inhibition is not involved. Alternatively, different receptor subtypes may be activated by sympathetic nerve stimulation and exogenous norepinephrine. In support of this explanation, we found that approximately 50% of the vasoconstrictor effect of sympathetic nerve stimulation (8 Hz) was blocked by prazosin, an alpha 1-adrenergic antagonist, but no further diminution of tone was seen with addiction of yohimbine, an alpha 2-adrenergic antagonist. In contrast, the vasoconstrictor response to exogenous norepinephrine was not affected by prazosin, while addition of yohimbine almost completely blocked the response. These findings suggest that muscle contraction selectively attenuates vasoconstriction mediated by junctional receptors in second-order arterioles.

Release of norepinephrine by sympathetic nerve stimulation from rabbit lungs

1978 ◽  
Vol 235 (6) ◽  
pp. H803-H808
Author(s):  
E. Y. Tong ◽  
A. A. Mathe ◽  
P. W. Tisher
Keyword(s):  
Electrical Stimulation ◽  
Pulmonary Artery ◽  
Monoamine Oxidase ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Sympathetic Nerves ◽  
Systemic Circulation ◽  
Inhibitory Mechanism ◽  
Sympathetic Nerve Stimulation ◽  
Mao Inhibitor

Rabbit lungs were perfused via the pulmonary artery and norepinephrine (NE) measured in the outflows. The basal NE level was approximately 3 ng/min. Electrical stimulation (50 V, 1 ms, 10 Hz) of the sympathetic nerves doubled the NE release. Hexamethonium (10(-4) and 10(-5) M) had no effect on the release of NE. Administration of a monoamine oxidase (MAO) inhibitor, pargyline (70 mg/kg) resulted in a 20-fold NE increase by nerve stimulation, implying that the bulk of the amine does not reach the systemic circulation due to an active MAO. Methacholine (1 and 10 micrograms/ml) inhibited NE release by nerve stimulation. This inhibition was abolished by atropine (5 micrograms/ml). It is suggested that a muscarinic inhibitory mechanism may regulate the NE release in the lung. PGE2 (100 ng/ml), but not PGS2alpha, (100 ng/ml), depressed NE release during nerve stimulation, whereas indomethacin (10 mg/kg) enhanced NE release before, during, and after nerve stimulation in seemingly normal animals. This indicates the existence of another presynaptic inhibitory mechanism for NE release in the lung: a PGE-mediated inhibition.

scholarly journals Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries

2012 ◽  
Vol 302 (3) ◽  
pp. H594-H602 ◽  
Author(s):  
Lydia W. M. Nausch ◽  
Adrian D. Bonev ◽  
Thomas J. Heppner ◽  
Yvonne Tallini ◽  
Michael I. Kotlikoff ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Adrenergic Receptor ◽  
Ryanodine Receptors ◽  
Electrical Field Stimulation ◽  
Sympathetic Nerves ◽  
Mesenteric Arteries ◽  
Sympathetic Nerve Stimulation ◽  
Voltage Dependent

It is generally accepted that the endothelium regulates vascular tone independent of the activity of the sympathetic nervous system. Here, we tested the hypothesis that the activation of sympathetic nerves engages the endothelium to oppose vasoconstriction. Local inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ signals (“pulsars”) in or near endothelial projections to vascular smooth muscle (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical field stimulation of sympathetic nerves induced an increase in endothelial cell (EC) Ca2+ pulsars, recruiting new pulsar sites without affecting activity at existing sites. This increase in Ca2+ pulsars was blocked by bath application of the α-adrenergic receptor antagonist prazosin or by TTX but was unaffected by directly picospritzing the α-adrenergic receptor agonist phenylephrine onto the vascular endothelium, indicating that nerve-derived norepinephrine acted through α-adrenergic receptors on smooth muscle cells. Moreover, EC Ca2+ signaling was not blocked by inhibitors of purinergic receptors, ryanodine receptors, or voltage-dependent Ca2+ channels, suggesting a role for IP3, rather than Ca2+, in VSM-to-endothelium communication. Block of intermediate-conductance Ca2+-sensitive K+ channels, which have been shown to colocalize with IP3 receptors in endothelial projections to VSM, enhanced nerve-evoked constriction. Collectively, our results support the concept of a transcellular negative feedback module whereby sympathetic nerve stimulation elevates EC Ca2+ signals to oppose vasoconstriction.

Impaired glucagon response to sympathetic nerve stimulation in the BB diabetic rat: effect of early sympathetic islet neuropathy

2003 ◽  
Vol 285 (5) ◽  
pp. E1047-E1054 ◽  
Author(s):  
Thomas O. Mundinger ◽  
Qi Mei ◽  
Dianne P. Figlewicz ◽  
Åke Lernmark ◽  
Gerald J. Taborsky
Keyword(s):  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Autoimmune Diabetes ◽  
Sympathetic Nerves ◽  
Diabetic Rat ◽  
Β Cells ◽  
Sympathetic Nerve Stimulation ◽  
Autoimmune Destruction ◽  
Functional Defect ◽  
6 Hydroxydopamine

We investigated the functional impact of a recently described islet-specific loss of sympathetic nerves that occurs soon after the autoimmune destruction of β-cells in the BB diabetic rat ( 35 ). We found that the portal venous (PV) glucagon response to sympathetic nerve stimulation (SNS) was markedly impaired in newly diabetic BB rats (BB D). We next found a normal glucagon response to intravenous epinephrine in BB D, eliminating the possibility of a generalized secretory defect of the BB D α-cell as the mediator of the impaired glucagon response to SNS. We then sought to determine whether the glucagon impairment to SNS in BB D was due solely to their loss of islet sympathetic nerve terminals or whether other effects of autoimmune diabetes contributed. We therefore reproduced, in nondiabetic Wistar rats, an islet nerve terminal loss similar to that in BB D with systemic administration of the sympathetic neurotoxin 6-hydroxydopamine. The impairment of the glucagon response to SNS in these chemically denervated, nondiabetic rats was similar to that in the spontaneously denervated BB D. We conclude that the early sympathetic islet neuropathy of BB D causes a functional defect of the sympathetic pathway to the α-cell that can, by itself, account for the impaired glucagon response to postganglionic SNS.

Atrial natriuretic factor attenuates sympathetic neuroeffector responses in hindlimb vasculature of rabbits

1989 ◽  
Vol 67 (9) ◽  
pp. 1101-1105 ◽  
Author(s):  
K. P. Patel
Keyword(s):  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Atrial Natriuretic Factor ◽  
Perfusion Pressure ◽  
Sympathetic Nerves ◽  
Sympathetic Nerve Stimulation ◽  
Arterial Infusion ◽  
Natriuretic Factor ◽  
Before And After ◽  
Atrial Natriuretic

To determine whether atrial natriuretic factor (ANF) affects vasoconstrictor responses to electrical stimulation of sympathetic nerves or intra-arterial norepinephrine (NE), changes in perfusion pressure were measured during lumbar sympathetic nerve stimulation (LSNS, 1–8 Hz), or administration of NE (50–200 ng), in an isolated constant flow-perfused hindlimb of chloralose-anesthetized rabbit before and after intra-arterial infusion of ANF (0.5 ng∙mL−1∙min−1). ANF significantly attenuated responses to LSNS (relative potency, RP = 0.65) and to NE (RP = 0.47). We conclude that ANF attenuates vasoconstrictor responses to both LSNS and NE. Thus ANF alters sympathetic nervous system mediated changes in vascular resistance possibly at the neuroeffector site.Key words: atrial natriuretic factor, sympathetic nerve stimulation, vasculature.

Alpha-adrenergic vasoconstriction in normal and hypoperfused myocardium during sympathetic nerve stimulation

1992 ◽  
Vol 263 (6) ◽  
pp. H1682-H1688 ◽  
Author(s):  
J. Westby ◽  
S. Birkeland ◽  
S. E. Rynning ◽  
O. L. Myking ◽  
J. Lekven ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Adrenergic Receptors ◽  
Left Ventricular ◽  
Regional Myocardial Blood Flow ◽  
Control Group ◽  
Coronary Perfusion ◽  
Sympathetic Nerve Stimulation

Coronary vasoconstriction mediated by postjunctional alpha 1- and alpha 2-adrenergic receptors was studied in normally perfused (control group) and left coronary hypoperfused (stenosis group) hearts of vagotomized, beta-blocked (propranolol) cats. Cardiac sympathetic nerve stimulation was combined with alpha 1- and subsequent alpha 2-adrenergic antagonism (doxazosin and SK &F 104078). Coronary perfusion pressure and heart rate were kept constant within groups; regional myocardial blood flow and cardiac output were obtained by means of microspheres with concomitant measurement of left ventricular myocardial oxygen consumption (MVO2). alpha 1-Adrenergic antagonism alone did not significantly alter blood flow in any wall layer in either group. Subsequent alpha 2-adrenergic antagonism increased epicardial as well as composite transmural flow in the stenosis group (P < 0.025). The inverse correlation between coronary resistance and MVO2 vanished in the stenosis group following alpha 1- and alpha 2-adrenergic antagonism. Maximal first derivative of the left ventricular pressure-time relation (dP/dt) and cardiac output were reduced simultaneously (P < 0.001). Hence, the significance of alpha 1- and alpha 2-adrenergic stimulation of inotropy and cardiac performance are augmented by myocardial hypoperfusion. Furthermore, alpha 2-adrenergic receptors are responsible for epicardial vasoconstriction in hypoperfused myocardium.

Effect of adenosine and glucagon on hepatic blood volume responses to sympathetic nerves

1991 ◽  
Vol 69 (1) ◽  
pp. 43-48 ◽  
Author(s):  
W. Wayne Lautt ◽  
Joshua Schafer ◽  
Dallas J. Legare
Keyword(s):  
Blood Volume ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Sympathetic Nerves ◽  
Liver Weight ◽  
Maximal Response ◽  
Venous Capacitance ◽  
Resistance Vessels ◽  
Capacitance Vessels

Hepatic blood volume responses were studied in cats using in vivo plethysmography. The maximal response (Rmax) to sympathetic nerve stimulation and to infusions of norepinephrine into the hepatic artery or portal vein was similar (12–14 mL expelled per liver in 2.9-kg cats; average liver weight, 76.8 ± 6.8 g). The ED50 for norepinephrine intraportal (0.44 ± 0.13) and intrahepatic arterial infusions (0.33 ± 0.08 μg∙kg−1∙min−1) were similar indicating equal access of both blood supplies to the capacitance vessels. Adenosine (2.0 mg∙kg−1∙min−1) did not cause significant volume changes but produced a mild (27%) suppression of Rmax due to nerve stimulation with no change in the frequency (3.4 Hz) needed to produce 50% of Rmax. Rmax tended (not statistically significant) to decrease during glucagon (1.0 μg∙kg−1∙min−1) infusion but the nerve frequency needed to produce 50% of Rmax rose to 5.6 Hz. Thus both adenosine and glucagon produced modulation of sympathetic nerve-induced capacitance responses without having significant effects on basal blood volume. Adenosine, by virtue of its marked effects on arterial resistance vessels (at substantially lower doses than those used here) and the relative lack of effect on venous capacitance vessels, may be useful for producing clinical afterload reduction without venous pooling.Key words: blood volume, capacitance, sympathetic nerves, adenosine, glucagon.

Canine liver releases neuropeptide Y during sympathetic nerve stimulation

1994 ◽  
Vol 266 (5) ◽  
pp. E804-E812 ◽  
Author(s):  
G. J. Taborsky ◽  
L. M. Beltramini ◽  
M. Brown ◽  
R. C. Veith ◽  
S. Kowalyk
Keyword(s):  
Neuropeptide Y ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
High Performance ◽  
Sympathetic Nerves ◽  
Sympathetic Nerve Stimulation ◽  
Predominant Form ◽  
Anesthetized Dogs ◽  
Minor Form ◽  
Hepatic Nerves

To determine whether the liver or gut releases neuropeptide Y (NPY) from their sympathetic nerves, we performed bilateral thoracic sympathetic nerve stimulation (BTSNS) in halothane-anesthetized dogs and calculated gut and liver NPY spillover. BTSNS markedly increased hepatic NPY spillover (delta = +32 +/- 8 ng/min) and arterial NPY concentration (delta = +220 +/- 56 pg/ml), despite no effect on gut NPY spillover (delta = +8 +/- 7 ng/min). To determine the liver's contribution to this increase of circulating NPY, hepatic nerves were selectively stimulated (HNS). Liver NPY spillover increased markedly (delta = +114 +/- 42 ng/min, P < 0.025) during HNS, causing a large increase of arterial NPY (delta = +586 +/- 237 pg/ml, P < 0.025). Using this ratio of liver spillover to arterial increments of NPY, we calculated that the liver makes a major contribution (70%) to circulating NPY levels during BTSNS. The predominant form of canine NPY coeluted with synthetic [Met17]NPY and the minor form of canine NPY coeluted with the oxidized form of [Met17]NPY on high-performance liquid chromatography. We therefore conclude that dog NPY is likely [Met17]NPY and that the liver, rather than the gut, is a major source of circulating NPY during sympathetic nerve stimulation and perhaps stress.

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