Nils O. Sjöstrand

Comparison of vascular effects of ropivacaine and lidocaine on isolated rings of human arteries.

Ropivacaine is a new local anaesthetic agent. Previous animal studies have indicated that vasoconstrictor effects are elicited by ropivacaine in vitro and subcutaneously and that it produces blanching of the skin if injected subcutaneously in humans.

Testicular atrophy and loss of nerve growth factor-immunoreactive germ cell line in rats exposed to n-hexane and a protective effect of simultaneous exposure to toluene or xylene

Testicular and germ cell line morphology in rats were studied 2 weeks, 10 months and 14 months after cessation of a 61-day inhalation exposure to 1000 ppm n-hexane. Androgen biosynthetic capacity of testis, testosterone blood concentration, vas deferens morphology and noradrenaline (NA) concentration, epididymal sperm morphology, and fertility were also studied. Severe testicular atrophy involving the seminiferous tubules with loss of the nerve growth factor (NGF) immunoreactive germ cell line was found. Total loss of the germ cell line was found in a fraction of animals up to 14 months post-exposure, indicating permanent testicular damage. No impairment of androgen synthesis or androgen dependent accessory organs was observed. Simultaneous administration of 1000 ppm n-hexane and 1000 ppm toluene, or 1000 ppm n-hexane and 1000 ppm xylene, did not cause germ cell line alterations or testicular atrophy. Toluene and xylene were thus found to protect from n-hexane induced testicular atrophy.

Nitric oxide-synthesizing neurons originating at several different levels innervate rat penis

While the crucial role of neurally produced nitric oxide in mediating penile erection is well established, the understanding of the peripheral neuroanatomy of the nitric oxide-ergic pathways is still incomplete. This study was designed to elucidate further the distribution of nitric oxide synthase, and its relation to the distribution of neuropeptides and tyrosine hydroxylase in all penis-projecting neural pathways. A triple-labelling technique was employed, with the retrograde tracer Fluoro Gold combined with neuropeptide immunohistochemistry and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, a marker of nitric oxide synthase. The presence within the penis of scattered nerve cell bodies exhibiting NADPH-diaphorase activity was revealed. Most (76%) of the penis-projecting neurons in the major pelvic ganglion exhibited NADPH-diaphorase activity and immunoreactivity to vasoactive intestinal peptide, while none of them contained tyrosine hydroxylase. Sympathetic paravertebral postganglionic neurons, in turn, contained tyrosine hydroxylase, but did not exhibit NADPH-diaphorase activity. In the afferent, sensory neurons projecting to the penis from the dorsal root ganglia, NADPH-diaphorase activity coexisted with immunoreactivity to both substance P (8%) and calcitonin gene-related peptide (26%). Preganglionic neurons originating in the spinal cord intermediolateral column at the thoracolumbar level T11-L3 terminated, not only in the major pelvic ganglion, but also within the penis. The majority (81%) of the penis-projecting neurons exhibited NADPH-diaphorase activity. The results indicate that the rat penis receives several different nitric oxide-ergic neural projections. It is therefore possible that nitric oxide affects penile erection at several neuronal levels.

Is glandular formation of nitric oxide a prerequisite for muscarinic secretion of fructose in the guinea-pig seminal vesicle?

The significance of nitric oxide (NO) formation in seminal secretion was studied in guinea-pig seminal vesicles. The nitric oxide synthase (NOS) activity was estimated and reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry was performed. Furthermore, cyclic guanosine 3,5-monophosphate (cGMP) concentration as well as fructose secretion from isolated vesicles was estimated. High Ca2+-dependent NOS activity as well as prominent glandular NADPH-diaphorase staining was found in the secretory epithelium. The NOS inhibitorsNG-nitrol-arginine methyl ester (L-NAME) andNG-nitrol-ar-ginine (L-NNA) inhibited carbachol-induced fructose secretion but the D-isomer to L-NAME had no effect. Whenl-arginine was administered together with L-NAME, no inhibitory effect on the carbachol-induced fructose secretion could be seen. Nerve-induced fructose secretion was also inhibited by L-NAME. The NO donor glyceryl trinitrate (GTN) increased the fructose secretion. Carbachol or GTN did not increase cGMP levels, nor was fructose secretion inhibited by a guanylate cyclase inhibitor (ODQ). Our results suggests that glandular NO production is a prerequisite for muscarinic fructose secretion in the seminal vesicle via a cGMP-independent pathway.

NADPH-diaphorase in glandular cells and nerves and its relation to acetylcholinesterase-positive nerves in the male reproductive tract of man and guinea-pig.

Abstract The presence of NADPH-diaphorase activity and acetylcholinesterase in the testis, epididymis, vas deferens, seminal vesicle, pelvic plexus, prostate and urethra of man and guinea-pig was investigated with the nitro blue NADPH technique and the thiocholine method, respectively. In human material NADPH-diaphorase activity was found in the Leydig cells, Sertoli cells and the epithelial linings of the rete testis, the excretory ducts, seminal vesicle, prostate and urethra. The guinea-pig material showed staining of the Leydig cells and spermatozoa and similar epithelial staining of the tract as man. Nerves beneath the epithelium and in the muscle layers of cauda epididymis, vas deferens, seminal vesicle, prostate and urethra were also stained. NADPH-diaphorase-positive nerve cells were seen in the pelvic plexus. Some cells also displayed acetylcholinesterase activity but others showed activity for only one of the enzymes or no activity for either enzyme. In the cauda epididymis, vas deferens, seminal vesicle, prostate and urethra acetylcholinesterase-positive nerve fibres formed a plexus beneath the secretory cells. It is concluded that NADPH-diaphorase, generally accepted as a nitric oxide synthase, is present in glandular cells of the male genital tract. The enzyme is also present in nerves, where it is partly co-localized with acetylcholinesterase.

Histochemical demonstration of nerve cell bodies in the retractor penis muscle and the penile artery of the bull

The presence of single nerve cell bodies and small ganglia in the retractor penis muscle and the penile artery of the bull was demonstrated by using antisera to neurofilament protein and neuron specific enolase. In the retractor penis muscle the findings were confirmed by staining for acetylcholinesterase. It was also shown that relaxation of strips of the retractor penis muscle induced by 70 microM acetylcholine was totally blocked by a 2.0 microM concentration of the ganglionic blocking drug chlorisondamine. The hypothesis is presented that the relaxation of the bovine retractor penis muscle and the bovine penile artery induced by nicotinic ganglionic stimulating drugs is at least in part mediated via receptors located on the nerve cell bodies described in this study.

Pathways for excitatory and inhibitory innervation to the guinea-pig tracheal smooth muscle.

The trachea receives excitatory cholinergic innervation from the vagus nerve and the stellate ganglion. Inhibitory adrenergic fibres have the same sources. Those in the vagus nerve probably derive from high vagosympathetic anastomoses. Nonadrenergic inhibitory fibres have a preganglionic vagal supply.

Inhibition of nicotine‐induced relaxation of the bovine retractor penis muscle by compounds known to have ganglion‐blocking properties

1 The relative potency in blocking the nicotine‐induced relaxation of the bovine retractor penis muscle (BRP) was estimated for 12 drugs known to have ganglion‐blocking properties. 2 The order of potency of the drugs studied was mecamylamine > chlorisondamine > pentolinium > propantheline > (+)‐tubocurarine > hexamethonium > emepronium > tetraethylammonium > glycopyrrolate > decamethonium > butylscopolamine > scopolamine. 3 The results conform well to those obtained with other pharmacological methods used for the estimation of ganglion‐blocking activity. 4 It is concluded that blockade of the nicotinic relaxation of the BRP can be used as an alternative method for quantitative assessment of ganglion‐blocking activity. 5 Advantages of this technique are that it discriminates well between antinicotinic and antimuscarinic activity and that it satisfies most or all ethical and economical demands. 6 It is also possible that this method has certain value in predicting whether a drug has enough ganglion‐blocking activity to be likely to cause impotence.

Effect of heavy physical training on the catecholamine content of the heart and adrenals of the guinea-pig

Ein langdauerndes Training bewirkt keine Herabsetzung der Catecholamine in Herz und Nebennieren des Meerschweinchens.

Chapter 13 – Nitric Oxide and the Neural Regulation of the Penis

Publisher Summary Nitric oxide synthase (NOS) is localized in nerves surrounding the deep penile artery and its helicine branches, as well as in nerves running to the smooth muscle of the walls of the cavernous spaces in rat. In the rat retractor penis muscle NOS-positive nerve fibers are detected with nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. Part of the neurogenic erectile response may be due to muscarinic stimulation of endothelial cells. It is found that through NO release from these cells, cholinergic nerves may act as indirect inhibitors of penile smooth muscle. NO release from the endothelium seems to be supplementary to NO release from nitrergic nerves, which seems to be obligatory for a full erectile response. The role of endothelial NO in penile erection is likely to be obtained when a compound blocking NO release from nerves, leaving neuronal release of acetylcholine and endothelial release of NO unimpaired, is developed.