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    Nitric oxide (NO) is a soluble, highly reactive gas formed by natural chemical and physical reactions in the atmosphere. It is also synthesized by certain animal and plant cells from the amino acid, L-arginine. Because it is so small and diffusible NO passes through cell membranes and is often used as a biological signal.

    In mammals NO helps to maintain blood pressure by dilating blood vessels, assists the immune system in killing invaders, and is a major factor in the control of penile erection (Viagra®, Levitra®, and Cialis® work by blocking an enzyme in the NO/cGMP pathway). In the brain, NO plays a role in development, neuron to neuron signaling, and probably contributes to the formation of memories.

    Nitric Oxide: History and Discovery

    History

    Sobrero Ascanio, a young Italian chemist interested in explosives, invented nitroglycerine in the late 1840s. The highly explosive liquid was produced by mixing glycerine with sulfuric and nitric acid and was considered too dangerous to be of any practical use. Alfred Nobel, while working in Paris in a private laboratory, met Ascanio and became very interested in the commercial application of nitroglycerine. There were enormous safety problems with nitroglycerine, but Nobel recognized it’s practical potential in construction use. At the time, Nobel’s father was providing equipment to the Russian army during the Crimean War (1853-1856). Young Nobel was asked to return to the family enterprise and together with his father, performed experiments to develop nitroglycerine as a useful explosive. It wasn’t until 1864 that Nobel was able to mass-produce nitroglycerine and soon discovered that by mixing the liquid with silica, the resulting paste could be shaped into rods suitable for insertion into drilling holes. In 1867, Nobel patented the material under the name of dynamite and soon after invented the blasting cap, the detonator that was ignited by lighting a fuse. The market for Nobel’s dynamite grew exponentially and by the time of his death in 1896, Nobel had founded factories and laboratories in more that 20 countries. When Nobel was taken ill with heart disease, his physician prescribed nitroglycerine known at that time to relieve chest pain but not known how. Nobel refused to take the drug knowing that it caused intense headaches. Nobel wrote just before his death: “It is ironical that I am now ordered by my physician to eat nitroglycerine.” It would take nearly 100 years before it would be discovered that nitroglycerine acts by releasing nitric oxide gas. In his will, Nobel’s had left his entire fortune to be used for Prizes in Physics, Chemistry, Physiology or Medicine, Literature and Peace. Today, the Nobel Foundation continues to manage the financial assets left by Nobel for this work and coordinates the efforts of the Prize-Awarding Institutions.

    Discovery

    In 1968 a young pharmacologist by the name of Louis Ignarro took a position at Geigy Pharmaceuticals heading their biochemical and inflammatory drug program. Dr. Ignarro had completed his postdoctoral work at the National Institutes of Health in the Laboratory of Chemical Pharmacology in the National Heart, Lung and Blood Institute. This allowed Ignarro to pursue his other research interests including the emerging field of cyclic nucleotides and was especially interested in cyclic guanosine mono phosphate (cyclic GMP). In 1973, Ignarro accepted an Assistant Professor of Pharmacology position at Tulane University School of Medicine in New Orleans and within two years had made significant contributions to the field of cyclic nucleotide research. He developed an interest in blood vessels while working on cyclic GMP in the heart and in 1977 read a paper by Dr. Ferid Murad, then at Stanford University, in which Murad showed that nitric oxide and various nitro compounds, including nitroglycerine, elevated cyclic GMP levels in various tissues. Murad speculated that nitroglycerine might act by releasing nitric oxide. Ignarro thought that nitric oxide might account for the vascular smooth muscle relaxing effect produced by nitroglycerine and that cyclic GMP might mediate the vasorelaxant effect of nitric oxide. The first published report of the capacity of nitric oxide to relax vascular smooth muscle appeared by Ignarro in 1979. In 1980 another pharmacologist by the name of Dr. Robert Furchgott demonstrated that blood vessels dilated only if the internal lining (the endothelium) was intact. He concluded that the endothelial cells must produce an unknown molecule that relaxes vascular smooth muscle and called his signal molecule EDRF or endothelium-derived relaxing factor. In 1984 it became clear to Ignarro that EDRF and nitric oxide possessed similar pharmacological and biochemical properties. In 1986 after a series of brilliant experiments, Ignarro concluded that EDRF was indeed nitric oxide and presented his findings in that same year at a vascular conference at the Mayo Clinic and later at an American Heart Association meeting in Dallas and in 1987 at a Federation meeting in Washington DC. It was now clear why nitric oxide was such a powerful vasorelaxant, a discovery that lead to an avalanche of studies creating an exciting new field in biological research.

    In 1985, Dr. Ignarro and his laboratory director moved to UCLA. Their research around elucidating the mechanism of action of smooth muscle relaxation continued and had expanded in 1989 to studying the effects of nitric oxide on vascular and non-vascular smooth muscle from corpus cavernosum erectile tissue. Ignarro realized that the neurotransmitter that mediated erections in the penis was completely unknown. The Ignarro group theorized that nitric oxide could be the neurotransmitter released from neurons that innervated the corpus cavernosum smooth muscle. If so, it would be expected that nitric oxide would permeate into the nearby vascular and nonvascular smooth muscle and cause the relaxation that accompanies the erectile response allowing for the engorgement of blood into the network of blood vessels in the corpus cavernosum and causing erection. Soon, experiments from human tissue showed that nitric oxide was the neurotransmitter responsible for erection and that patients with impotence suffer from an impairment in the nitric oxide cyclic GMP pathway in erectile tissue.

    The Nobel Prize

    By the time 1986 had come to an end, it was known that our blood vessels could manufacture nitric oxide, the active principle of nitroglycerine. New roles for nitric oxide were being discovered on a weekly basis from the ensuing avalanche of research. In 1986 there were only a dozen papers in total published on nitric oxide and by 1996, publications on nitric oxide were running at over 7,000 per year. The implications from the discovery were enormous and the observation by Ignarro and others made it possible to understand what protects the cardiovascular system against pathological conditions such as hypertension, stroke, coronary artery disease, gastrointestinal ulcers, vascular complications of diabetes and even erectile dysfunction. In 1991, nitric oxide was named Molecule of the Year by Science magazine and in1998, the discovery of this simple molecule was awarded the Nobel Prize in Physiology of Medicine and hailed as a major advance in medicinal science. Upon awarding Drs. Furchgott, Ignarro and Murad the Prize, the Nobel Assembly at the Karolinska Institutet in Stockholm, Sweden, cited that:
    “Nitric Oxide (NO) is a gas that transmits signals in the organism. Signal transmission [transduction] by a gas that is produced by one cell, penetrates through membranes and regulates the function of another cell represents an entirely new principle for signaling in biological systems. The discoverers of NO as a signal molecule are awarded this year’s Nobel Prize.”

    Women are from Venus

    The female sex organ (clitoris) primarily consists of a small erectile body composed of two fused corpora cavernosa. The glans is a small rounded body composed of erectile tissue and is homologous to the glans penis of the male. While both the exact mechanism of engorgement and erection of the clitoris remains unknown and the nervous innervation of the female genitalia certainly not identical to that of the male, both mechanism and nervous innervation would be expected to be similar to the male. To that extent, nitric oxide would also be expected to have a profound effect on the vascular and nonvascular smooth muscle surrounding the blood vessels traversing the clitoris. Once released from the neurons innervating the erectile tissue, nitric oxide would work by relaxing the smooth muscle surrounding the blood vessels causing a relaxant effect and allowing for an increased flow of blood and eventual engorgement.

    “I can’t get no satisfaction…”

    Sildenafil (Viagra®) Tadalafil (Cialis®), and Vardenafil (Levitra®) have been shown to be effective in men suffering from erectile dysfunction (ED), but have not proven effective in women most likely due to the presence of a different form of cyclic GMP phosphodiesterase in women. While many have tried, few companies have succeeded in developing products for women to help enhance sexual pleasure. Men have come to rely primarily on Viagra, a drug that is not without risk and side effects.

    Working with a principle member of Dr. Louis Ignarro’s Nobel Prize-winning laboratory, the company has developed a topical gel for women containing key elements (enzymes and cofactors) known to be involved in both generating nitric oxide and initiating the cascade of events that lead to blood vessel dilation. That gel is called "Enjoy Now". When applied topically to the clitoral area, the product helps stimulate the body’s own enzyme systems to produce nitric oxide locally, dilating local blood vessels and increasing blood flow to the area. The resulting effect should enhance the sexual experience while producing a warm, tingling sensation that may last up to an hour. Because every woman’s biology is different, results will vary depending on mood or concomitant use of other drugs.

    Enjoy Now®- Sexual Enhancement
    Stimulating and Lubricating Gel For Women

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    What is Enjoy Now?
    Enjoy Now is a non-prescription gel that is formulated to:
    • Promote sexual arousal
    • Provide a cool, tingling sensation upon application
    • Provide a silky, non-sticky lubrication
    Enjoy Now was developed by the former laboratory director for one of the 1998 Nobel Prize winning scientists in Physiology or Medicine. This advancement in science led to the discovery of Viagra.

    Enjoy Now is a personal lubricant and is intended to reduce vaginal dryness and pain or discomfort during sexual intercourse while promoting the desired effect of stimulating sexual arousal and responsiveness.

    Enjoy Now contains a proprietary blend of naturally occurring elements and cofactors that aid in the production of nitric oxide, the molecule responsible for dilating blood vessels.

    Enjoy Now is easy to use. Prior to sexual activity, gently massage Enjoy Now onto the clitoris and into the nearby tissue, including the vagina. While results vary among women, you can expect the sensation of Enjoy Now to begin to work within minutes after application.

    Enjoy Now is a water-based lubricant with a pleasant spearmint flavor and is safe if ingested. While most water-based lubricants can be safely used with condoms, Enjoy Now has not been tested with condoms. Enjoy Now is not a form of birth control nor will it prevent the spread of sexually transmitted diseases. You should take precautions and avoid contact with the eyes. If you have a preexisting medical condition, consult with your physician before using Enjoy Now. If irritation should occur, discontinue use and consult your physician. Do not use Enjoy Now if you are pregnant. Enjoy Now contains a nitric oxide generating system, L-arginine, and menthol.

    Coming Soon: Read what women are saying about Enjoy Now.

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    “Reignite the passion and enjoy sex there’s no tomorrow…Enjoy Now”


    @seXfactor.info 2004


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