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

Hayashida, H; Fujimoto, Hiroshi; Yoshida, Kazuhide; Tomoyoshi, T; Okamura, Tomio; Toda, Noboru

doi:10.1254/jjp.72.231

Cited by 10 publications

(14 citation statements)

References 26 publications

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“…These results indicate that hypercapnia fails to stimulate the release of endotheliumderived NO, but acts directly on arterial smooth muscle and induces vasodilatation, possibly by lowering extracellular pH and activation of the Na ϩ pump. A further study has demonstrated that the cerebroarterial relaxation induced by electrical stimulation, nicotine, substance P, and exogenous NO is potentiated in the hypercapnic media, possibly due to a decreased degradation of NO (Toda et al, 1996a). Taken together, under resting conditions in vivo, the vasodilator response to NO continuously released from the endothelium and perivascular nitrergic nerves may be enhanced by hypercapnic acidosis.…”

Section: Pharmacology Of Neurogenic No In Blood Vesselmentioning

confidence: 90%

“…However, no evidence was shown that the molecules liberated from perivascular nerves dilated the arteries. The possible contribution of the peptides and acetylcholine synthesized and released from the nerve as mediators or neurotransmitters was excluded in dog and monkey cerebral arteries by the fact that the response to nerve stimulation was not influenced by capsaicin (Okamura and Toda, 1994c), by muscarinic receptor antagonists (Toda, 1975(Toda, , 1982, by removal of the endothelium (Toda and Okamura, 1990b,c), or in arteries made tachyphylactic to the peptides under consideration (Toda, 1982;Okamura et al, 1989;Toda and Okamura, 1996a). In some studies with feline cerebral arteries, atropine depressed the neurogenic relaxation, suggesting that acetylcholine is one of the neurotransmitters (Bevan et al, 1982a,b).…”

Section: A From Nonadrenergic Noncholinergic Nerve To Nitrergic Nervementioning

confidence: 99%

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The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

2003

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Section: Pharmacology Of Neurogenic No In Blood Vesselmentioning

confidence: 90%

Section: A From Nonadrenergic Noncholinergic Nerve To Nitrergic Nervementioning

confidence: 99%

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

2003

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“…9,10 In addition to this mechanical restriction of the venous outflow, there is an active regulation of venous resistance, and several vasoconstrictor and vasodilator stimuli can regulate penile venous tone to the same extent as arterial and cavernous smooth muscle. [11][12][13][14][15][16][17] The active control of penile veins probably accommodates blood flow from the penis to the hemodynamic changes that take place in the CC during erection and detumescence.…”

Section: Introductionmentioning

confidence: 99%

Physiological regulation of penile arteries and veins

2007

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Recent experimental evidence suggests that arterial insufficiency precedes the structural and functional changes in corpora cavernosa (CC) leading to organic erectile dysfunction (ED). The present review gives an overview of the physiological factors involved in the regulation of penile vasculature. Sympathetic nerves maintain flaccidity and tonically released noradrenaline induces vasoconstriction of both arteries and veins through a 1 -and a 2 -postsynaptic receptors and downregulates its own release and that of nitric oxide (NO) through a 2 -presynaptic receptors. The sympathetic cotransmitter neuropeptide Y (NPY) modulates noradrenergic vasoconstriction in penile small arteries by both enhancing and depressing noradrenaline contractions through Y 1 -and Y 2 -postsynaptic and a NO-independent atypical endothelial receptor, respectively. Activation of a 1 -adrenoceptors involves both Ca 2 þ influx through L-type and receptor-operated Ca 2 þ channels (ROC) and Ca 2 þ sensitization mechanisms mediated by protein kinase C (PKC), tyrosine kinases (TKs) and Rho kinase (RhoK). In addition, RhoK can regulate Ca 2 þ entry in penile arteries upon receptor stimulation. Vasodilatation of penile arteries and large veins during erection is mediated by neurally released NO. The subsequent increased arterial inflow to the cavernosal sinoids and shear stress on the endothelium lining penile arteries activates endothelial NO production through Akt phosphorylation of endothelial NO synthase (eNOS). NO stimulates guanylate cyclase and increased cyclic guanin 3 0 -monophosphate (cGMP) levels in turn activate protein kinase G (PKG), which enhances K þ efflux through Ca 2 þ -activated (K Ca ) and voltage-dependent Ca 2 þ (K v ) channels in penile arteries and veins, respectively. PKG-mediated decrease in Ca 2 þ sensitivity and its regulation by RhoK remains to be clarified in penile vasculature. Phosphodiesterase type 5 (PDE5) inhibitors are potent vasodilators of penile resistance arteries and increase the content and effects of basally released endothelial NO. Endothelium-dependent relaxations of penile small arteries also include an endothelium-derived hyperpolarizing factor (EDHF)-type response, which is impaired in diabetes and hypertension-associated ED. Locally produced contractile and relaxant prostanoids regulate penile venous and arterial tone, respectively. The latter activates prostaglandin I (IP) and prostaglandin E (EP) receptors coupled to adenylate cyclase and to the increase of cyclic adenosine monophosphate (cAMP) levels, which in turn stimulates K þ efflux through ATPsensitive K þ (K ATP ) channels. There is a crosstalk between the cGMP and cAMP signaling pathways in penile small arteries. Relevant issues such as the mechanisms underlying the excitationsecretion coupling of the endothelial cells, as well as those involved in cell proliferation and vascular remodeling of the penile vasculature remain to be elucidated. In addition, only few studies have investigated the changes in structure and function of penile a...

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“…A recent report about quality of life in the hypertensive patients treated chronically with calcium antagonists suggests that the amlodipine-treated group has more sexual symptom distress compare to the nifedipinetreated group (20). However, this does not directly mean that L-plus N-type calcium antagonists have an inhibitory effect on penile erection, because the penile artery supplying blood to the corpus cavernosum is mainly innervated with noradrenergic vasoconstrictor nerves (21).…”

Section: Discussionmentioning

confidence: 99%

Effects of Calcium Antagonists on the Nitrergic Nerve Function in Canine Corpus Cavernosum

Okamura

Fujioka

Ayajiki

2001

Japanese Journal of Pharmacology

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ABSTRACT-Effects of calcium antagonists on nitrergic nerve function were examined in the isolated canine corpus cavernosum. In the cavernous strips precontracted with phenylephrine, transmural electrical stimulation elicited frequency-dependent (2 -5 Hz) relaxations that were abolished by N G -nitro-L-arginine (10 -5 M), a nitric oxide (NO) synthase inhibitor; 1H[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10 -6 M), a soluble guanylate cyclase inhibitor; and tetrodotoxin (3´10 -7 M). The relaxations were not affected by treatment with nifedipine or nicardipine (10 -8 -10 -6 M), L-type specific calcium channel inhibitors, but were significantly inhibited by amlodipine or cilnidipine, inhibitors of L-plus N-type calcium channels, in a concentration-related manner (10 -7 -10 -6 M). All of the inhibitors used did not affect the relaxations induced by exogenous NO (acidifed NaNO2). These findings suggest that N-type, but not L-type, calcium channels are responsible for increasing cytosolic free calcium, a prerequisite for the synthesis of NO, in the nitrergic dilator nerves innervating the corpus cavernosum. Keywords: Corpus cavernosum, Nitrergic nerve, Transmural electrical stimulation, Calcium antagonist, Smooth muscle relaxationPenile erection is induced by relaxation of the smooth muscle of penile corpus cavernosum and increased pooling of blood in the corpus (1). Autonomic nerves play an important role in the control of the function. Recently, nitric oxide (NO) released from nitrergic nerves is considered to be mainly responsible for the erection in rats (2), rabbits (3) and dogs (4, 5). Potentiation of the function by sildenafil, a selective inhibitor of cyclic GMP specific phosphodiesterase V, and its potent therapeutic effect on erectile dysfunction also demonstrate the involvement of the endogenous NO-cyclic GMP pathway in human penile erection (6).Although importance of nitrergic nerve function in the penile erection has been recognized, the mechanism underlying the synthesis / release of neurogenic NO is not clarified in the corpus cavernosum. Our findings from experiments with cerebral arteries, which are also innervated mainly with nitrergic dilator nerves, suggest that production of neurogenic NO is calcium-and calmodulin-dependent (7,8), and N-, but not L-, type calcium channels are involved in the response (7, 9).

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

Cited by 10 publications

References 26 publications

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

Physiological regulation of penile arteries and veins

Effects of Calcium Antagonists on the Nitrergic Nerve Function in Canine Corpus Cavernosum

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