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Book: Nitric oxide and the regulation of the peripheral circulation

Kadowitz, Philip J.

(Nitric oxide in biology & medicine ; 1)

2000

Author's details	Philip J. Kadowitz ... ed
Series title	Nitric oxide in biology & medicine ; 1 Nitrogen oxides in biology and medicine
Collection	Nitrogen oxides in biology and medicine
Keywords	Peripherer Blutkreislauf ; Regulation ; Stickstoffmonoxid
Language	English
Size	X, 362 S. : graph. Darst.
Publisher	Birkhäuser
Publishing place	Boston u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT011222617
ISBN	0-8176-4046-0 ; 3-7643-4046-0 ; 978-0-8176-4046-0 ; 978-3-7643-4046-9
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: The Nitric Oxide Pathway in Pulmonary Vascular Disease.

Klinger, James R / Kadowitz, Philip J

The American journal of cardiology

2017 Volume 120, Issue 8S, Page(s) S71–S79

Abstract: Nitric oxide is an endogenous pulmonary vasodilator that is synthesized from L-arginine in pulmonary vascular endothelial cells by nitric oxide synthase and diffuses to adjacent vascular smooth muscle cells where it activates soluble guanylyl cyclase. ... ...

Abstract	Nitric oxide is an endogenous pulmonary vasodilator that is synthesized from L-arginine in pulmonary vascular endothelial cells by nitric oxide synthase and diffuses to adjacent vascular smooth muscle cells where it activates soluble guanylyl cyclase. This enzyme converts GTP to cGMP which activates cGMP dependent protein kinase leading to a series of events that decrease intracellular calcium and reduce vascular muscle tone. Nitric oxide is an important mediator of pulmonary vascular tone and vascular remodeling. A number of studies suggest that the bioavailability of nitric oxide is reduced in patients with pulmonary vascular disease and that augmentation of the nitric oxide/cGMP pathway may be an effective strategy for treatment. Several medications that target nitric oxide/cGMP signaling are now available for the treatment of pulmonary hypertension. This review explores the history of nitiric oxide research, describes the major NO synthetic and signaling pathways and discusses a variety of abnormalities in NO production and metabolism that may contribute to the pathophysiology of pulmonary vascular disease. A summary of the clinical use of presently available medications that target nitric oxide/cGMP signaling in the treatment of pulmonary hypertension is also presented.
MeSH term(s)	Cyclic GMP/physiology ; Humans ; Hypertension, Pulmonary/etiology ; Hypertension, Pulmonary/physiopathology ; Hypertension, Pulmonary/therapy ; Nitric Oxide/physiology ; Signal Transduction ; Soluble Guanylyl Cyclase/physiology
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; Soluble Guanylyl Cyclase (EC 4.6.1.2) ; Cyclic GMP (H2D2X058MU)
Language	English
Publishing date	2017-10-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2017.06.012
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Article ; Online: Angina pectoris: current therapy and future treatment options.

Parikh, Raj / Kadowitz, Philip J

Expert review of cardiovascular therapy

2014 Volume 12, Issue 2, Page(s) 175–186

Abstract: Angina pectoris is the consequence of an inequality between the demand and supply of blood to the heart. Angina manifests itself as chest pain or discomfort and is a common complaint of patients in the hospital and in the clinic. There are, in fact, ... ...

Abstract	Angina pectoris is the consequence of an inequality between the demand and supply of blood to the heart. Angina manifests itself as chest pain or discomfort and is a common complaint of patients in the hospital and in the clinic. There are, in fact, roughly half a million new cases of angina per year. Chest pain, while having many etiologies, is generally considered to be most lethal when related to a cardiac cause. In this review, the authors outline the current medical and surgical therapies that are used in the management of angina. Highlights of the various clinical trials that have assisted in the investigation of these therapies are summarized also. Then, the authors provide a focused review of the novel therapy options for angina that are currently being explored. From new medical treatments to revised surgical techniques to the discovery of stem cell therapy, many innovative options are being investigated for the treatment of angina.
MeSH term(s)	Angina Pectoris/physiopathology ; Angina Pectoris/therapy ; Animals ; Cardiovascular Agents/pharmacology ; Cardiovascular Agents/therapeutic use ; Chest Pain/etiology ; Clinical Trials as Topic ; Humans ; Stem Cell Transplantation/methods
Chemical Substances	Cardiovascular Agents
Language	English
Publishing date	2014-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2192343-7
ISSN	1744-8344 ; 1477-9072
ISSN (online)	1744-8344
ISSN	1477-9072
DOI	10.1586/14779072.2014.880339
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Article: Stimulators of soluble guanylyl cyclase: future clinical indications.

Nossaman, Bobby D / Kadowitz, Philip J

The Ochsner journal

2013 Volume 13, Issue 1, Page(s) 147–156

Abstract: Background: Soluble guanylyl cyclase (sGC) is expressed in mammalian cytoplasm and catalyzes the synthesis of the second messenger guanosine 3',5'-monophosphate (cGMP) involved in important physiological functions such as relaxation of vascular smooth ... ...

Abstract	Background: Soluble guanylyl cyclase (sGC) is expressed in mammalian cytoplasm and catalyzes the synthesis of the second messenger guanosine 3',5'-monophosphate (cGMP) involved in important physiological functions such as relaxation of vascular smooth muscle, inhibition of platelet aggregation, modulation of inflammation, and control of vascular permeability. sGC is the intracellular receptor for nitric oxide (NO) and the active moiety in traditional organic nitrate therapy, recently as an inhalant in the intensive care unit and experimentally in improving microcirculatory flow in shock. However, dysfunction of the heme moiety on sGC occurs in a number of cardiovascular diseases, which reduces NO effectiveness. Methods: In this review, we examine animal studies and early clinical trials on agents that can directly stimulate sGC and may have future clinical application in cardiovascular disease and in perioperative care. Conclusions: Animal and early clinical studies have shown that sGC stimulator agents have great promise for treating cardiopulmonary disorders and may also have a role in modulating the inflammatory response observed in perioperative care.
Language	English
Publishing date	2013-03-26
Publishing country	United States
Document type	Journal Article
ISSN	1524-5012
ISSN	1524-5012
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Article ; Online: A review of current therapies used in the treatment of congestive heart failure.

Parikh, Raj / Kadowitz, Philip J

Expert review of cardiovascular therapy

2013 Volume 11, Issue 9, Page(s) 1171–1178

Abstract: Congestive heart failure is the leading cause of hospitalizations for patients older than 65 years. There are almost 700,000 new cases of heart failure annually and re-hospitalization rates are as high as 50% within the first few months of initial ... ...

Abstract	Congestive heart failure is the leading cause of hospitalizations for patients older than 65 years. There are almost 700,000 new cases of heart failure annually and re-hospitalization rates are as high as 50% within the first few months of initial discharge. These statistics translate to healthcare costs that nearly reached US$40 billion in 2010. Understanding the therapeutic agents that can not only help decrease mortality and morbidity but also decrease the rate of re-hospitalizations is vital in the management of congestive heart failure. Here, the authors highlight the various classes of drugs used in the treatment of heart failure. They then provide a focused review examining the multiple clinical trials that have emphasized the evaluation of mortality, morbidity and hospitalization rates in heart failure patients who are receiving the different types of therapeutic agents.
MeSH term(s)	Adrenergic beta-Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Heart Failure/mortality ; Heart Failure/therapy ; Heart-Assist Devices ; Humans ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Treatment Outcome
Chemical Substances	Adrenergic beta-Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Mineralocorticoid Receptor Antagonists
Language	English
Publishing date	2013-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2192343-7
ISSN	1744-8344 ; 1477-9072
ISSN (online)	1744-8344
ISSN	1477-9072
DOI	10.1586/14779072.2013.816478
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Article ; Online: Current therapies for premature ejaculation.

Gur, Serap / Kadowitz, Philip J / Sikka, Suresh C

Drug discovery today

2016 Volume 21, Issue 7, Page(s) 1147–1154

Abstract: Premature ejaculation (PE) subjectively affects 20-30% of men globally. Until recently, understanding of PE was hampered by the absence of a widely accepted definition, paucity of evidence-based clinical studies, and the absence of an appropriate animal ... ...

Abstract	Premature ejaculation (PE) subjectively affects 20-30% of men globally. Until recently, understanding of PE was hampered by the absence of a widely accepted definition, paucity of evidence-based clinical studies, and the absence of an appropriate animal model. Here, we elaborate on the current definition of PE, its pathogenesis, currently available therapies, and future treatment prospects. Most treatments for PE are 'off-label' and include selective serotonin reuptake inhibitors (SSRIs), topical anesthetics, tramadol, and phosphodiesterase type 5 (PDE5) inhibitors. Such knowledge of the benefit and limitations of each treatment will help to direct future drug design and formulations.
Language	English
Publishing date	2016-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2016.05.004
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Article ; Online: Aging and sexual health: getting to the problem.

Kaya, Ecem / Sikka, Suresh C / Kadowitz, Philip J / Gur, Serap

The aging male : the official journal of the International Society for the Study of the Aging Male

2017 Volume 20, Issue 2, Page(s) 65–80

Abstract: Erectile dysfunction (ED) is one of the most common disorders in male and is often associated with other age-related comorbidities. The aging process affects the structural organization and function of penile erectile components such as smooth muscle ... ...

Abstract	Erectile dysfunction (ED) is one of the most common disorders in male and is often associated with other age-related comorbidities. The aging process affects the structural organization and function of penile erectile components such as smooth muscle cell and vascular architecture. These modifications affect penile hemodynamics by impairing cavernosal smooth muscle cell relaxation, reducing penile elasticity, compliance and promoting fibrosis. This review aims to identify the mechanisms of ED in the penile aging process in experimental and clinical data. It also highlights areas that are in need of more research. The search strategies yielded total records screened from PubMed. Clarification of the molecular mechanisms that accompanies corpus cavernosum aging and aging-associated ED will aid new perspectives in the development of novel mechanism-based therapeutic approaches. Age is not a limiting factor for ED medical management, and it is never too late to treat. Hypogonadism should be managed regardless of age, and synergistic effects have been found during testosterone (T) replacement therapy when used along with oral phosphodiesterase-5 (PDE-5) inhibitors. Therefore, the clinical management of ED related to aging can be done by therapeutic interventions that include PDE-5 inhibitors, and other pharmacological treatments.
Language	English
Publishing date	2017-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2108146-3
ISSN	1473-0790 ; 1368-5538
ISSN (online)	1473-0790
ISSN	1368-5538
DOI	10.1080/13685538.2017.1295435
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Article: The metabolism and significance of homocysteine in nutrition and health.

Kumar, Avinash / Palfrey, Henry A / Pathak, Rashmi / Kadowitz, Philip J / Gettys, Thomas W / Murthy, Subramanyam N

Nutrition & metabolism

2017 Volume 14, Page(s) 78

Abstract: An association between arteriosclerosis and homocysteine (Hcy) was first demonstrated in 1969. Hcy is a sulfur containing amino acid derived from the essential amino acid methionine (Met). Hyperhomocysteinemia (HHcy) was subsequently shown in several age- ...

Abstract	An association between arteriosclerosis and homocysteine (Hcy) was first demonstrated in 1969. Hcy is a sulfur containing amino acid derived from the essential amino acid methionine (Met). Hyperhomocysteinemia (HHcy) was subsequently shown in several age-related pathologies such as osteoporosis, Alzheimer's disease, Parkinson's disease, stroke, and cardiovascular disease (CVD). Also, Hcy is associated with (but not limited to) cancer, aortic aneurysm, hypothyroidism and end renal stage disease to mention some. The circulating levels of Hcy can be increased by defects in enzymes of the metabolism of Met, deficiencies of vitamins B
Language	English
Publishing date	2017-12-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2160376-5
ISSN	1743-7075
ISSN	1743-7075
DOI	10.1186/s12986-017-0233-z
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Article: The role of the RhoA/rho-kinase pathway in pulmonary hypertension.

Nossaman, Bobby D / Kadowitz, Philip J

Current drug discovery technologies

2009 Volume 6, Issue 1, Page(s) 59–71

Abstract: The small GTP-binding protein, RhoA, and its downstream effector protein, rho-kinase, have been implicated in the pathogenesis of a number of cardiovascular diseases. The activation of rho-kinase is involved in the development of increased vascular tone, ...

Abstract	The small GTP-binding protein, RhoA, and its downstream effector protein, rho-kinase, have been implicated in the pathogenesis of a number of cardiovascular diseases. The activation of rho-kinase is involved in the development of increased vascular tone, endothelial dysfunction, inflammation, and restenosis; and that the inhibition of rho-kinase has been shown to have a beneficial effect in a variety of cardiovascular disorders. It is our hypothesis that rho-kinase inhibitors promote vasodilation independent of the mechanism that increases vasoconstrictor tone and moreover, the RhoA/rho-kinase pathway has a role in the regulation of smooth muscle tone under physiological conditions. The objective of this review is to improve our current understanding of the role of RhoA/rho-kinase pathway in the regulation of vasoconstrictor tone and the use of rho-kinase inhibitors in the treatment of cardiovascular disorders with an emphasis on pulmonary hypertension.
MeSH term(s)	Animals ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/physiopathology ; Humans ; Hypertension, Pulmonary/drug therapy ; Hypertension, Pulmonary/physiopathology ; Protein Kinase Inhibitors/pharmacology ; Vasoconstriction/drug effects ; Vasodilation/drug effects ; rho-Associated Kinases/antagonists & inhibitors ; rho-Associated Kinases/metabolism ; rhoA GTP-Binding Protein/metabolism
Chemical Substances	Protein Kinase Inhibitors ; rho-Associated Kinases (EC 2.7.11.1) ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2009-03-03
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	1570-1638
ISSN	1570-1638
DOI	10.2174/157016309787581057
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Article ; Online: Modulation of soluble guanylate cyclase for the treatment of erectile dysfunction.

Lasker, George F / Pankey, Edward A / Kadowitz, Philip J

Physiology (Bethesda, Md.)

2013 Volume 28, Issue 4, Page(s) 262–269

Abstract: Nitric oxide (NO) is the principal mediator of penile erection, and PDE-5 inhibitors are the first-line agents used to treat erectile dysfunction (ED). When NO formation or bioavailability is decreased by oxidative stress and PDE-5 inhibitors are no ... ...

Abstract	Nitric oxide (NO) is the principal mediator of penile erection, and PDE-5 inhibitors are the first-line agents used to treat erectile dysfunction (ED). When NO formation or bioavailability is decreased by oxidative stress and PDE-5 inhibitors are no longer effective, a new class of agents called soluble guanylate cyclase (sGC) stimulators like BAY 41-8543 will induce erection. sGC stimulators bind to the normally reduced, NO-sensitive form of sGC to increase cGMP formation and promote erection. The sGC stimulators produce normal erectile responses when NO formation is inhibited and the nerves innervating the corpora cavernosa are damaged. However, with severe oxidative stress, the heme iron on sGC can be oxidized, rendering the enzyme unresponsive to NO or sGC stimulators. In this pathophysiological situation, another newly developed class of agents called sGC activators can increase the catalytic activity of the oxidized enzyme, increase cGMP formation, and promote erection. The use of newer agents that stimulate or activate sGC to promote erection and treat ED is discussed in this brief review article.
MeSH term(s)	Cyclic GMP/physiology ; Erectile Dysfunction/drug therapy ; Erectile Dysfunction/physiopathology ; Guanylate Cyclase/physiology ; Guanylate Cyclase/therapeutic use ; Humans ; Male ; Morpholines/therapeutic use ; Nitric Oxide/physiology ; Penile Erection/physiology ; Phosphodiesterase 5 Inhibitors/therapeutic use ; Pyrimidines/therapeutic use ; Treatment Outcome
Chemical Substances	BAY 41-8543 ; Morpholines ; Phosphodiesterase 5 Inhibitors ; Pyrimidines ; Nitric Oxide (31C4KY9ESH) ; Guanylate Cyclase (EC 4.6.1.2) ; Cyclic GMP (H2D2X058MU)
Language	English
Publishing date	2013-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2158667-6
ISSN	1548-9221 ; 1548-9213
ISSN (online)	1548-9221
ISSN	1548-9213
DOI	10.1152/physiol.00001.2013
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