scholarly journals Relaxation Effect of Patchouli Alcohol in Rat Corpus Cavernous and Its Underlying Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fangjun Chen ◽  
Yifei Xu ◽  
Jing Wang ◽  
Xufeng Yang ◽  
Hongying Cao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Soluble Guanylate Cyclase ◽  
Corpus Cavernosum ◽  
Relaxation Effect ◽  
Calcium Antagonism ◽  
Nitric Oxide Signaling ◽  
Patchouli Alcohol ◽  
Cox Inhibitor ◽  
Oxide Synthase

In this study, we investigated the relaxation effect and mechanisms of patchouli alcohol (PA) on rat corpus cavernosum. Corpus cavernosum strips were used in organ baths for isometric tension studies. The results showed that PA demonstrated concentration-dependent relaxation effect on rat corpus cavernosum. The relaxant response to PA was not influenced by tetrodotoxin and atropine while it was significantly inhibited by removal of endothelium. L-NG-nitroarginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor) significantly inhibited relaxation response to PA, whereas indomethacin (COX inhibitor) had no effect on PA-induced relaxation. The treatment of endothelium-deprived corpus cavernosum with several potassium channel blockers including tetraethylammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide had no effect on PA-induced relaxation. Endothelium-deprived corpus cavernosal contractions induced by cumulative addition of Ca2+ to high KCl solution without CaCl2 were significantly inhibited by PA. Also, PA improved relaxant capacity of sildenafil in rat corpus cavernosum. In addition, the perfusion with PA significantly increased the levels of cGMP and expression of mRNA and protein of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, intracavernous injection of PA enhanced the rise in intracavernous pressure in rats during cavernosal nerve electric stimulation. In conclusion, PA relaxed the rat corpus cavernosum attributed to both endothelium-dependent and -independent properties. While the former component was mostly involved in nitric oxide signaling pathway, the endothelium-independent mechanism involved in PA-induced relaxation was probably linked to calcium antagonism.

scholarly journals Modulation of Opioid Actions by Nitric Oxide Signaling

2009 ◽  
Vol 110 (1) ◽  
pp. 166-181 ◽  
Author(s):  
Noboru Toda ◽  
Shiroh Kishioka ◽  
Yoshio Hatano ◽  
Hiroshi Toda ◽  
David S. Warner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Glial Cells ◽  
Withdrawal Syndrome ◽  
Therapeutic Agents ◽  
Nitric Oxide Signaling ◽  
Endogenous Nitric Oxide ◽  
Oxide Synthase ◽  
New Strategies

Nitric oxide (NO) plays pivotal roles in controlling physiological functions, participates in pathophysiological intervention, and is involved in mechanisms underlying beneficial or untoward actions of therapeutic agents. Endogenous nitric oxide is formed by three isoforms of nitric oxide synthase: endothelial, neurogenic and inducible. The former two are constitutively present mainly in the endothelium and nervous system, respectively, and the latter one is induced by lipopolysaccharides or cytokines mainly in mitochondria and glial cells. Constitutively formed nitric oxide modulates the actions of morphine and related analgesics by either enhancing or reducing antinociception. Tolerance to and dependence on morphine or its withdrawal syndrome are likely prevented by nitric oxide synthase inhibition. Information concerning modulation of morphine actions by nitric oxide is undoubtedly useful in establishing new strategies for efficient antinociceptive treatment and for minimizing noxious and unintended reactions.

Abstract 1415: Activation of Soluble Guanylate Cyclase Regulates Phosphodiesterase 5A Localization and Restores Anti-adrenergic Action of Sildenafil despite Nitric Oxide Synthase Inhibition

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Takahiro Nagayama ◽  
Manling Zhang ◽  
Eiki Takimoto ◽  
David A Kass
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Soluble Guanylate Cyclase ◽  
Synergistic Effects ◽  
Adrenergic Stimulation ◽  
Adrenergic Activity ◽  
Oxide Synthase

Background: We have shown that inhibition of cyclic GMP-phosphodiesterase 5A (PDE5A) by sildenafil (SIL) blunts cardiomyocyte β-adrenergic stimulation, but this effect depends on the activity of endothelial nitric oxide synthase (eNOS) to generate a specific pool of cyclic GMP. PDE5A normally localizes at Z-bands in myocytes, but localization is more diffuse in cells with eNOS chronically inhibited. Here, we tested whether the influence of eNOS on PDE5A localization and anti-adrenergic action depends upon cyclic GMP. Methods and Results: Mouse in vivo hemodynamics were assessed by pressure-volume analysis. Isoproterenol (ISO: 20 ng/kg/min, iv ) stimulated contractility was inhibited by SIL (100 μg/kg/min, iv ), however this did not occur in mice given N w -nitro-L-arginine methyl ester (L-NAME: 1 mg/mL in drinking water for 1 week) to inhibit NOS. Myocytes transfected with an adenoviral vector encoding a fusion protein (PDE5A-DSred) in vivo were subsequently isolated and examined for PDE5A/α-actinin localization. Normal cells showed strong co-localization, whereas L-NAME-treated cells had diffuse PDE5A distribution. If L-NAME was stopped for 1-wk washout, SIL regained anti-adrenergic activity, and PDE5A z-band localization was restored. If L-NAME was continued but combined with Bay 41– 8543 (BAY: 30 mg/kg/day, po ), a soluble guanylate cyclase (sGC) activator, both PDE5A localization and SIL anti-adrenergic action were also restored. Chronic L-NAME suppressed phosphorylation of vasodilator-stimulated protein (VASP), a marker of protein kinase G (PKG) activity, in hearts acutely exposed to ISO+SIL. After L-NAME washout or L-NAME+BAY, VASP phosphorylation with ISO+SIL was restored. Conclusion: NOS-dependent modulation of both PDE5A sarcomere localization and anti-adrenergic activity depends upon sGC-derived cyclic GMP, and is linked to PKG activation. This suggests sGC activators may have synergistic effects with PDE5A inhibitors.

Student Research Award 1994: Nitric Oxide in the Rat Vestibular System

1994 ◽  
Vol 111 (4) ◽  
pp. 430-438 ◽  
Author(s):  
Andrew Harper ◽  
William R. Blythe ◽  
Carlton J. Zdanski ◽  
Jiri Prazma ◽  
Harold C. Pillsbury
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Amino Acid ◽  
Nitric Oxide Synthase ◽  
Vestibular System ◽  
Soluble Guanylate Cyclase ◽  
Excitatory Amino Acid ◽  
Nerve Fibers ◽  
Guanosine Monophosphate ◽  
Oxide Synthase

Nitric oxide is known to function as a neurotransmitter in the central nervous system. It is also known to be involved in the control nervous system excitatory amino acid neurotransmission cascade. Activation of excitatory amino acid receptors causes an influx of calcium, which activates nitric oxide synthase. The resulting increase in intracellular nitric oxide activates soluble guanylate cyclase, leading to a rise in cyclic guanosine monophosphate. The excitatory amino acids giutamate and aspartate are found in the vestibular system and have been postulated to function as vestibular system neurotransmitters. Although nitric oxide has ben investigated as a neurotransmitter in other tissues, no published studies have examined the role of nitric oxide in the vestibular system. Neuronal NADPH-dlaphorase has been characterized as a nitric oxide synthase. This enzyme catalyzes the conversion of L-arginine to l-citrulline, producing nitric oxide during the reaction. We used a histochemical stain characterized by Hope et al. (Proc Natl Acad Sci 1991;88:2811) as specific for neuronal nitric oxide synthase to localize the enzyme in the rat vestibular system. An Immunocytochemical stain was used to examine rat Inner ear tissue for the presence of the enzyme's end product, l-citrulline, thereby demonstrating nitric oxide synthase activity. Staining of vestibular ganglion sections showed nitric oxide synthase presence and activity in ganglion cells and nerve fibers. These results Indicate the presence of active nitric oxide synthase in these tissues and suggest modulation of vestibular neurotransmission by nitric oxide.

PGE2, via EP3 receptors, regulates brain nitric oxide synthase in the perinatal period

1998 ◽  
Vol 275 (6) ◽  
pp. R1812-R1821 ◽  
Author(s):  
Isabelle Dumont ◽  
Krishna G. Peri ◽  
Pierre Hardy ◽  
Xin Hou ◽  
Ana Katherine Martinez-Bermudez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Perinatal Period ◽  
Adult Brain ◽  
Newborn Rats ◽  
Cox Inhibitor ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Brain Nitric Oxide ◽  
Nnos Expression

We tested the hypothesis that high prostaglandin levels during the perinatal period might regulate brain nitric oxide synthase (nNOS) expression. nNOS and cyclooxygenase (COX)-2 mRNAs were higher in brain cortex and the periventricular area of newborn rats and pigs compared with adult brain. Nitric oxide synthase activity was also 2.5- to 4-fold higher in newborn than in adult brain. Administration of nonselective COX inhibitor ibuprofen or COX-2 inhibitor nimesulide every 8 h for 24 h to newborn rats and pigs reduced prostaglandin levels and caused comparable reductions in nNOS mRNA, protein, and activity to levels of adults; COX inhibitor-induced changes were prevented by cotreatment with PGE2 analog, 16,16-dimethyl-PGE2, and agonist for the EP3 receptor of PGE2, sulprostone, but not by PGI2 analog carbaprostacyclin, PGD2, EP1 receptor agonist 17-phenyl trinor-PGE2, and EP2 agonist butaprost. Concordant observations were made in vitro and revealed that nNOS expression (detected by NADPH diaphorase reactivity) mostly present in neurons of the deeper cortical layers was reduced by COX inhibitor, and this effect was prevented by EP3agonist. In conclusion, high levels of PGE2 in neonatal brain contribute to the increased expression of nNOS by acting on EP3 receptors; this positive interaction between PGE2 and nNOS might be required physiologically for normal brain development.

IMMUNOCYTOCHEMICAL DISTRIBUTION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE (eNOS) IN HUMAN CORPUS CAVERNOSUM

1999 ◽  
pp. 221 ◽  
Author(s):  
Andreas Stanarius ◽  
Stefan Uckert ◽  
Stefan A. Machtens ◽  
Christian G. Stief ◽  
Gerald Wolf ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Corpus Cavernosum ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide
Sign in / Sign up

Export Citation Format

Share Document