Erection and NO override the vasoconstrictive effect of α-adrenergic stimulation in the rat penile vasculature (original) (raw)
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Endothelin-1-induced vasoconstriction is inhibited during erection in rats
American journal of physiology. Regulatory, integrative and comparative physiology, 2001
Recent evidence indicates that endothelin-1 (ET-1) might be a principal vasoconstrictor in the penis. We report that ET-1 injection into the cavernous sinuses before erection sharply reduced the magnitude of subsequent erections. Corpus cavernosum pressure-to-mean arterial pressure ratios (CCP/MAP), with maximal ganglionic stimulation, were 0.62 +/- 0.05 before ET-1 injection and 0.31 +/- 0.05 after, indicating that ET-1 acted as a vasoconstrictor. When ET-1 was injected during a maximal neurally induced erection, the ability of ET-1 to attenuate subsequent erections was diminished (CCP/MAP 0.75 +/- 0.02 before ET-1, 0.61 +/- 0.03 after). At submaximal stimulation voltages, injection of ET-1 during erection also attenuated its vasoconstrictive effect. Similarly, when ET-1 was injected during erection induced by intracavernosal injection of the nitric oxide (NO) donor NOR-1, subsequent erections were not significantly suppressed (CCP/MAP 0.53 +/- 0.04 before ET-1, 0.45 +/- 0.04 after...
Regulation of Adrenergic Activity in Penile Corpus Cavernosum
The Journal of Urology, 1989
The regulation of adrenergic activity in the penis was investigated by studying human and rabbit corpus cavernosum strips in organ chambers and measuring the release of norepinephrine from adrenergic nerve terminals. Electrical field stimulation of corporal strips caused frequency-dependent contractions which were potentiated by cocaine and attenuated by the alpha1 adrenoceptor antagonist prazosin (10-7 M), but not by the alpha2 adrenoceptor antagonist rauwolscine (10-7 M). Norepinephrine caused concentration-dependent contractions of corporal strips, which were attenuated by prazosin and rauwolscine. Acetylcholine and physostigmine attenuated adrenergic nerve mediated contractions and also significantly reduced electrically-induced norepinephrine release. These effects were reversed by atropine. Atropine alone enhanced electrically-induced norepinephrine release. Rauwolscine inconsistently enhanced adrenergic nerve mediated contractions but augmented norepinephrine release caused by electrical stimulation. The alpha2 adrenoceptor agonist clonidine inhibited electrically-induced norepinephrine release. Vasoactive intestinal polypeptide (VIP) attenuated adrenergically-mediated contractions, but had no effect on electrically-induced release of norepinephrine. It is concluded that: 1) contraction of corporal smooth muscle is mediated by postjunctional alpha1 adrenoceptors; 2) adrenergic activity is modulated by prejunctional alpha2 adrenoceptors and cholinergic nerves via prejunctional muscarinic receptors; and 3) the putative nonadrenergic noncholinergic neurotransmitter, VIP, has no apparent role in the regulation of adrenergic nerves.
Pharmacology of penile erection
Pharmacological reviews, 2001
Erection is basically a spinal reflex that can be initiated by recruitment of penile afferents, but also by visual, olfactory, and imaginary stimuli. The reflex involves both autonomic and somatic efferents and is modulated by supraspinal influences. Several central transmitters involved in the erectile control have been identified. Dopamine, acetylcholine, nitric oxide (NO), and peptides, such as oxytocin and adrenocorticotropic/alpha-melanocyte-stimulating hormone, seem to have a facilitatory role, whereas serotonin may be either facilitatory or inhibitory, and enkephalins are inhibitory. Peripherally, the balance between contractant and relaxant factors controls the degree of contraction of the smooth muscle of the corpora cavernosa and determines the functional state of the penis. Noradrenaline contracts both corpus cavernosum and penile vessels via stimulation of alpha(1)-adrenoceptors. Neurogenic NO is considered the most important factor for relaxation of penile vessels and c...
British Journal of Pharmacology, 1990
The pathophysiology of impotence related to vascular smooth muscle dysfunction in the male corpus cavernosum was studied on human isolated erectile tissue (HET). Studies were conducted on 140 sections of HET obtained from 38 male patients undergoing surgery for implantation of penile prostheses to correct underlying erectile dysfunction. 2 Spontaneous myotonic oscillations were characteristic of greater than 90% of all HET preparations at 37°C. These spontaneous oscillations were markedly attenuated by indomethacin, BW755C, nifedipine, removal of extracellular Ca2+, or lower temperatures (< 320C), but were not sensitive to inhibition by atropine, phentolamine or tetrodotoxin. Our data suggest that the oscillations may, at least in part, result from the generation and/or release of a stable cyclo-oxygenase product and a consequent increase in transmembrane Ca2 + influx. 3 The phenylephrine-induced contractions in HET may be reliably assayed up to 24 h after surgical removal, without significant alterations in the EC50, maximum response (E,,^x) or slope index of the steady-state concentration-response curve to phenylephrine. 4 The competitive and surmountable nature of the antagonism of phenylephrine-induced contractions by prazosin and yohimbine allowed calculation of antagonist dissociation constants. The calculated pKb values for prazosin and yohimbine, respectively, were 9.47 + 0.49 and 5.54 + 0.22. The rank order of agonist potency in HET was: noradrenaline = phenylephrine > clonidine. These data indicate the presence of a population of membrane receptors that are predominantly of the a,-adrenoceptor subtype.
Effects of intracavernous administration of adrenomedullin on erectile function in rats
Peptides, 2001
We have reported that adrenomedullin (AM)-induced vasodilation is at least in part nitric oxide (NO)-cGMP-dependent in the rat. Although it is well known that NO is much involved in the erectile function, it is controversial as to whether AM influences the erectile function. Thus, we examined the effects of AM on intracavernous pressure (ICP) during penile erection. The left carotid artery of rats was cannulated to monitor of mean arterial pressure (MAP). Bipolar electrodes were positioned on the cavernous nerve. The right cavernous body was cannulated with a needle connected to a pressure transducer to monitor ICP. Electrical stimulation (ES) increased ICP in a voltage-dependent manner. Elevation of ICP continued during ES. The intracavernous injection of 0.5 nmol AM significantly potentiated ES-induced increases in both maximal developed ICP/MAP and area under the curve (ICP trace; AUC). Since AM slightly lowered MAP, ICP was normalized by MAP. i.v. administration of N -nitro-L-arginine, a NO synthase inhibitor, markedly decreased AM/ES-induced ICP elevation. However, in the presence of E-4021, a cGMP-specific phosphodiesterase inhibitor, AM further increased both ICP/MAP and AUC. These results suggest that a NO-cGMP pathway is involved in the regulation of AM-induced rat cavernous vasorelaxation.
Inhibition of tonic contraction--a novel way to approach erectile dysfunction
Journal of andrology
Experiments from this laboratory have demonstrated that vasoconstriction in the cavernosal circulation is mediated, in part, by the RhoA/Rho-kinase calcium-sensitization pathway. When RhoA/Rho-kinase signaling is inhibited with Y-27632 in cavernosal smooth muscle, the intracavernosal pressure (ICP) is markedly elevated without a significant change in mean arterial pressure (MAP). To explain how erection can occur in the presence of this strong vasoconstrictive signal, we have suggested that nitric oxide (NO) induces vasodilation, leading to erection by directly inhibiting activity of the RhoA/Rho-kinase pathway. The following discussion summarizes the importance of Rho-kinase signaling in the erectile response and introduces its possible clinical value in 2 animal models of erectile dysfunction (ED) (severe hypogonadism and hypertension). In addition, we suggest that topical application of Y-27632 could be an effective mode of treatment for ED.
British Journal of Pharmacology, 2002
Eects of A-322312 (a 1B-adrenoceptor (AR) antagonist), A-119637 (a 1D-AR antagonist), prazosin (non-selective a 1-AR antagonist), and yohimbine (a 2-AR antagonist) were studied in rat corpus cavernosum (CC) and cavernous artery (Acc) preparations. Eects of intracavernous (i.c.) or intraperitoneal (i.p.) administration of a 1-AR antagonists on apomorphine-induced erections were investigated. 2 A-119637 attenuated electrically induced contractions in isolated CC (7logIC 50 ; 8.12+0.15), and relaxed noradrenaline (NA)-contracted preparations by more than 90% at 10 77 M. At the same concentration, the 7logEC 50 value for NA in Acc was altered from 6.79+0.07 to 4.86+0.13. In the CC and Acc, prazosin similarily inhibited contractile responses. 3 Inhibitory eects of A-322312 (10 77 M) in electrically activated CC were 32.3+5.1%, whereas no eect on concentration-response curves for NA was observed in the Acc. Yohimbine (10 78 M and 10 77 M), enhanced electrically-induced contractions in isolated CC by 20 to 50%. At 10 76 M, inhibitory eects of yohimbine were obtained. 4 A-119637 (0.3 mmol kg 71 , i.p.) tripled the number of erections, and produced a 6 fold increase in the duration of apomorphine-induced erectile responses. A-322312, prazosin, or yohimbine did not enhance erections induced by apomorphine. None of the a 1-AR antagonists signi®cantly increased ICP upon i.c. administration. Decreases in blood pressure were seen with A-119637 and prazosin. 5 The present ®ndings show that there is a functional predominance of the a 1D-AR subtype in the rat erectile tissue, and that blockade of this receptor facilitates rat penile erection induced by a suboptimal dose of apomorphine.
Urology, 2003
Objectives. To evaluate the effects of the nitric oxide (NO)-donating compounds sodium nitroprusside (SNP), S-nitroso-glutathione (GSNO), S-nitroso-N-acetylcysteine (SNAC), S-nitroso-N-acetylcysteineethylester (SNACET), and linsidomine (SIN-1) on the adrenergic tension of isolated human seminal vesicle strip preparations. The significance of the NO-cyclic guanosine monophosphate (cGMP) pathway in the regulation of smooth muscle tone in the human genitourinary tract has been well established. However, information on the significance of NO-mediated signal transduction in the functional control of the mammalian seminal vesicles is still sparse. Methods. Seminal vesicle strip preparations were applied to an organ bath system under standard conditions. Tension was induced by the addition of 10 M norepinephrine. After stable tension plateaus had been reached, the drugs were added in a cumulative manner (0.01 to 100 M) and the isometric responses of the tissue registered. The effects of the compounds on the phasic contractility of the tissue preparations were also evaluated. The adenylyl cyclase-stimulating agent forskolin was used as a reference compound known to interfere with the cyclic adenosine monophosphate pathway. Results. Adrenergic tension was dose dependently attenuated by the drugs. The rank order of potency, from greater to lesser, was GSNO, SNAC, SNP, SIN-1, forskolin, and SNACET. The rank order (from greater to lesser) with regard to the inhibitory effects of the compounds on the frequency of phasic contractions of the tissue induced by the addition of norepinephrine was GSNO, SNAC, SNP, and SIN-1; the effects of SIN-1, forskolin, and SNACET on the frequency of contractions were nearly equipotent.