Abstract:SUMMARY1. The haemodynamics of erection were elucidated in the anaesthetized dog by analysing in quantitative terms the changes of penile arterial inflow, venous outflow and tissue volume during graded pelvic nerve stimulation. The study also provides information on possible neurotransmitter mechanisms of the erectile response.2. Erection evoked by pelvic nerve stimulation appeared to result from two main circulatory events: first, there was a prompt dilatation of the penile 'resistance vessels', causing a gre… Show more
“…Although it has been suggested that vasoactive intestinal polypeptide (VIP) is the neurotransmitter of NANC nerves in canine penile erection (Anderson et al 1984), canine penile erection induced by cavernous nerve stimulation was not abolished, but modified by VIP-anitibody (Juenemann et al…”
We investigated the pharmacological effects of adenosine on canine penile erection in vivo. Intracavernous injection of adenosine induced a full erection, which was unaffected by hexamethonium and atropine. The erectile response induced by adenosine was augmented by intracavernous pretreatment with dipyridamole and markedly depressed by theophylline. The erectile response induced by cavernous nerve stimulation was also enhanced by dipyridamole and reduced by theophylline. The combination of acetylcholine and adenosine, when injected intracavernously, induced a full erection, and the effect of these drugs was not additive but synergistic. These results suggest that penile erection induced by adenosine is due to a direct relaxing effect on cavernous smooth muscle. We propose that adenosine plays a cooperative role with acetylcholine and also has a physiological role as a neuromodulator in canine penile erection. adenosine ; dipyridamole ; theophylline ; penile erection ; dog Adenosine and adenine nucleotides are known to be potent vasodilators in various vascular beds and they play a significant role in physiological functions and pathological states (Snyder 1985). The inhibitory effect of adenosine is selectively antagonized by theophylline at the site of the adenosine receptor (Hayashi et al. 1978) and is potentiated by dipyridamole, which inhibits adenosine uptake (Hayashi et al. 1985).Penile erection is mediated by three types of neurological control : adrenergic, cholinergic and non-adrenergic and non-cholinergic (NANC) systems (Saenz de Tejada et al. 1988a). Although it has been suggested that vasoactive intestinal polypeptide (VIP) is the neurotransmitter of NANC nerves in canine penile erection (Anderson et al. 1984), canine penile erection induced by cavernous nerve stimulation was not abolished, but modified by VIP-anitibody (Juenemann et al.
“…Although it has been suggested that vasoactive intestinal polypeptide (VIP) is the neurotransmitter of NANC nerves in canine penile erection (Anderson et al 1984), canine penile erection induced by cavernous nerve stimulation was not abolished, but modified by VIP-anitibody (Juenemann et al…”
We investigated the pharmacological effects of adenosine on canine penile erection in vivo. Intracavernous injection of adenosine induced a full erection, which was unaffected by hexamethonium and atropine. The erectile response induced by adenosine was augmented by intracavernous pretreatment with dipyridamole and markedly depressed by theophylline. The erectile response induced by cavernous nerve stimulation was also enhanced by dipyridamole and reduced by theophylline. The combination of acetylcholine and adenosine, when injected intracavernously, induced a full erection, and the effect of these drugs was not additive but synergistic. These results suggest that penile erection induced by adenosine is due to a direct relaxing effect on cavernous smooth muscle. We propose that adenosine plays a cooperative role with acetylcholine and also has a physiological role as a neuromodulator in canine penile erection. adenosine ; dipyridamole ; theophylline ; penile erection ; dog Adenosine and adenine nucleotides are known to be potent vasodilators in various vascular beds and they play a significant role in physiological functions and pathological states (Snyder 1985). The inhibitory effect of adenosine is selectively antagonized by theophylline at the site of the adenosine receptor (Hayashi et al. 1978) and is potentiated by dipyridamole, which inhibits adenosine uptake (Hayashi et al. 1985).Penile erection is mediated by three types of neurological control : adrenergic, cholinergic and non-adrenergic and non-cholinergic (NANC) systems (Saenz de Tejada et al. 1988a). Although it has been suggested that vasoactive intestinal polypeptide (VIP) is the neurotransmitter of NANC nerves in canine penile erection (Anderson et al. 1984), canine penile erection induced by cavernous nerve stimulation was not abolished, but modified by VIP-anitibody (Juenemann et al.
“…4,7 Many investigators have suggested that the 28 aminoacid peptide VIP is one of the NANC neurotransmitter(s) in the trabecular smooth muscle of the corpus cavernosum. 8,9 In support of this, several observations revealed that VIP immunoreactive fibres densely innervate the trabecular smooth muscle and that VIP elicits relaxation of the trabecular smooth muscle. 10 The results of some in vivo studies demonstrated that VIP can induce an increase in ICP in various species.…”
In accordance with the data reporting the identification of nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) positive nerve fibres in the trabecular meshwork of the corpus cavernosum, we suggest that nitric oxide (NO) and VIP may serve complementary physiological roles in penile erection. Therefore SIN-1 and VIP were administered alone and in combination in an in vivo rabbit model. All rabbits revealed basal pressure values of 5 -8 cm H 2 O intracavernously. In the rabbits intracavernously (i.c.) injected with SIN-1 alone and VIP alone, no adequate erectile responses were observed. Whereas, in the group intracavernously injected with the combination of SIN-1 þ VIP, erectile responses with mean maximal intracavernous pressure (max. ICP) 52.8 ( AE 13.2) cm H 2 O were noted. These pressure elevations do not statistically diverge (P > 0.05) than the ones obtained in the control group administered i.c. injections of the combination of papaverine=phentolamine (mean max. ICP 51 ( AE 14.73) cm H 2 O). Referring to our results, we conclude that the combined use of SIN-1 þ VIP could play an important role in the physiological treatment of erectile dysfunction.
“…Correlative in vivo investigation has provided a critical adjunct to af®rm the erectogenic effects of potential pharmacotherapies. Examples include vasoactive intestinal peptide, 62,63 prostaglandin E1, 64 apomorphine, 65 nitric oxide donors, 66 vasoactive peptides, 67 sildena®l, 29,68 nitrosylated alpha-adrenergic receptor antagonists, 69 and potassium-ATP channel openers. 70 In the course of these studies, animal models have shown the effectiveness of multiple routes of drug administration in vivo, which include General use of animal models AL Burnett intravascular, oral, topical, subcutaneous, intraperitoneal, intracorporal, intraurethral, intrathecal and intracerebral routes.…”
Section: Therapeutic Applications Of Animal Modelsmentioning
confidence: 99%
“…58 Pharmacological investigation has been applied extensively to animal models, both in relationship to novel therapeutic options and to techniques for administering therapeutic agents. Diverse in vitro methodologies using isolated erectile tissue from many animal species including bull, 59 dog, 60 rabbit, 61 rat, 62 and mouse 26,27,30 have been employed to evaluate the presence and mechanisms of action of putative erectile neurotransmitters and other effectors of the erectile response. Correlative in vivo investigation has provided a critical adjunct to af®rm the erectogenic effects of potential pharmacotherapies.…”
Section: Therapeutic Applications Of Animal Modelsmentioning
Animals have consistently assumed a major place in the scienti®c developments of erection physiology, and in fact the use of animal models can be claimed to have inaugurated this ®eld as a true scienti®c discipline. The roots of the science of sexual medicine do not coincide with its practice, which conceivably pertains to aphrodisiacs and other sexual stimulants touted as therapies since antiquity. Rather, the beginnings of scienti®c study in the ®eld are ®ttingly identi®ed with the pioneering experimental work of Eckhard, who in 1863 showed the importance of the pelvic nerves for erectile function by performing electrical stimulation of these`nervi erigentes' in the anesthetized dog to elicit penile erection. 1 The understanding that penile erection is displayed under neurophysiological control was con®rmed and re®ned towards the late nineteenth century by the work of several important researchers in the ®eld, including Mu È ller, Bernard, Gaskell, and Langley and Anderson, who applied animal models to show the gross anatomic locations and physiological relevance of nerves coursing from spinal levels to the pelvis for regulation of penile erection: the mostly antagonistic parasympathetic and sympathetic autonomic nerves, and the somatic nerves. 2,3 The impressive methods of electrophysiological experimentation in the mammalian pelvis combined with extirpative lesioning of spinal out¯ow tracts employed by many of these early scientists continue to be applied similarly in modern research studies.Other pre-eminent control systems involved in erection physiology, accepted now as basic tenets of the ®eld, are known substantially from animal experimentation. The physiology of genital blood ow as an essential component of the erectile response was discovered early and established in concert with electrophysiological investigation. Research progress in recent decades has built on observations of the role of the vascular system and taken a major focus towards understanding penile vascular smooth muscle properties and penile hemodynamics. The central nervous system control of penile erection has been explored somewhat less intensively thus far, although early neuropharmacological and lesioning methods have suggested that hypothalamic and limbic pathways exert predominant in¯uences in the erectile response. 2,4,5 Scienti®c study in animals has also supported the erection regulatory basis involving circulating male hormones, evidenced by the fact that androgen loss such as that following castration leads to erectile impairment and, oppositely, androgen replacement promotes recovery of erectile function. 6,7 Role of animal models to study penile erectionThe selection of animal models for study in the ®eld of sexual dysfunction research has undergone an evolutionary process much like the ®eld itself. The relatively large size and thus inherent technical feasibility of certain animals such as dogs and monkeys lent these species as the primary models for in vivo investigation of penile erection until recent times. Thei...
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