Synthetic nitrovasodilators are effective, in vitro, in relaxing penile tissue from impotent men: the findings and their implications

1989 ◽  
Vol 67 (1) ◽  
pp. 78-81 ◽  
Author(s):  
Jeremy P. W. Heaton
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Venous Occlusion ◽  
Isometric Tension ◽  
Smooth Muscle Relaxation ◽  
Clinical Criteria ◽  
Erectile Tissue ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

Normal penile erectile function is dependent on arterial adequacy, appropriate venous occlusion, neurohumoral factors, and finally the relaxation of penile cavernous trabecular smooth muscle. The present experiments were designed to test whether compounds related to endothelium-derived relaxing factor have a role in penile smooth muscle relaxation and whether this role is preserved in clinically impotent tissue. Isometric tension experiments were conducted using strips of human tissue (appropriately obtained) from patients found to be impotent by clinical criteria. Glyceryl trinitrate and isosorbide dinitrate produced maximal relaxations of 66 and 63%, respectively, in tissues contracted with norepinephrine: 50% relaxation was observed at 6 × 10−7 and 8 × 10−5 M, respectively. The finding of a relaxant response to synthetic nitrovasodilators in "impotent" tissue implies that (i) complete end organ (smooth muscle) failure is not always, if ever, seen, (ii) endothelium-derived factors probably play a role in erectile tissue parallel with their role in other vascular tissues, (iii) more proximal factors may be responsible for clinical impotence, and (iv) synthetic nitrovasodilators may have a role in the therapy of clinical impotence.Key words: penis, erection, nitrovasodilators, endothelium-derived relaxing factor, human.

The role of lysolecithin in the relaxation of vascular smooth muscle

1987 ◽  
Vol 7 (10) ◽  
pp. 783-789 ◽  
Author(s):  
Richard J. Bing ◽  
Maythem Saeed
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Relaxing Factor ◽  
Aortic Strip ◽  
Rabbit Aortic Strip ◽  
Ionic Detergent ◽  
Endothelium Derived Relaxing Factor ◽  
Triton X

The effect of lysolecithin (lysophosphatidylcholine) on the relaxation of rabbit aortic strip closely resembled that produced by acetylcholine (ACh) which releases the endothelium-derived relaxing factor (EDRF). Relaxation induced by lysolecithin depended on the presence of endothelium and was inhibited by hemoglobin and methylene blue. It appeared to be mediated by the second messenger, c-GMP. Lysolecithin induced relaxation was slower but more persistent than that resulting from the endothelium-derived relaxing factor (EDRF) produced by acetylcholine (ACh). Like lysolecithin, Triton X-100, a non-ionic detergent, also preferentially relaxed aortic strips with intact endothelium. The results demonstrate the importance of phospholipids derived from cell membranes in vascular smooth muscle relaxation. Endothelium-derived relaxing factors appear as a group of heterogeneous substances.

scholarly journals The Use of Vasoactive Drugs in the Treatment of Male Erectile Dysfunction: Current Concepts

2020 ◽  
Vol 9 (9) ◽  
pp. 2987
Author(s):  
George T. Kedia ◽  
Stefan Ückert ◽  
Dimitrios Tsikas ◽  
Armin J. Becker ◽  
Markus A. Kuczyk ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Erectile Dysfunction ◽  
Cyclic Gmp ◽  
Muscle Relaxation ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Smooth Muscle Relaxation ◽  
Vasoactive Drugs ◽  
Erectile Tissue ◽  
Orally Active

It is widely accepted that disorders of the male (uro)genital tract, such as erectile dysfunction (ED) and benign diseases of the prostate (lower urinary tract symptomatology or benign prostatic hyperplasia), can be approached therapeutically by influencing the function of both the vascular and non-vascular smooth muscle of the penile erectile tissue or the transition zone/periurethral region of the prostate, respectively. As a result of the discovery of nitric oxide (NO) and cyclic guanosine monophosphate (GMP) as central mediators of penile smooth muscle relaxation, the use of drugs known to increase the local production of NO and/or elevate the intracellular level of the second messenger cyclic GMP have attracted broad attention in the treatment of ED of various etiologies. Specifically, the introduction of vasoactive drugs, including orally active inhibitors of the cyclic GMP-specific phosphodiesterase (PDE) 5, has offered great advantage in the pharmacotherapy of ED and other diseases of the genitourinary tract. These drugs have been proven efficacious with a fast on-set of action and an improved profile of side-effects. This review summarizes current strategies for the treatment of ED utilizing the application of vasoactive drugs via the oral, transurethral, topical, or self-injection route.

Acute exposure to cholesterol increases arterial nitroprusside- and endothelium-mediated relaxation

1993 ◽  
Vol 264 (1) ◽  
pp. C32-C39 ◽  
Author(s):  
R. A. Bialecki ◽  
T. N. Tulenko
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Free Cholesterol ◽  
Molar Ratio ◽  
Relaxing Factor ◽  
Arterial Relaxation ◽  
Endothelium Derived Relaxing Factor ◽  
Arterial Endothelium ◽  
Muscle Responses

The effect of cholesterol enrichment on arterial relaxation was studied by evaluating sodium nitroprusside (SNP)- and endothelium-mediated relaxation of isolated rabbit carotid artery. Arterial segments were perfused in vitro (4 h) with cholesterol-rich liposomes consisting of free cholesterol (FC) and phospholipid (PL) in a 2:1 molar ratio. Ring segments from arteries exposed to cholesterol-rich liposomes exhibited a 60% increase (P < 0.01) in FC content without affecting PL content. Cholesterol-enrichment was associated with a twofold increase (r = 0.92, P < 0.05) in acetylcholine- and A23187-induced endothelium-mediated relaxation. Bioassay of endothelium-derived relaxing factor(s) (EDRF) after cholesterol exposure indicated that EDRF half-life and/or release increased (P < 0.05) threefold. A trend (P = 0.07) toward increased smooth muscle cell sensitivity to EDRF after cholesterol enrichment was also observed. Cholesterol enrichment increased (P < 0.05) sensitivity to SNP 12-fold, and this difference was further augmented (P < 0.01) twofold with endothelium removal. Cholesterol enrichment had no effect on relaxation to N2,2'-O-dibutyrylguanosine 3',5'-cyclic monophosphate. These data indicate that acute cholesterol enrichment increases EDRF activity from arterial endothelium and increases smooth muscle responses to both EDRF and SNP.

Cigarette smoke extract contracts isolated porcine coronary arteries by superoxide anion-mediated degradation of EDRF

1994 ◽  
Vol 266 (3) ◽  
pp. H874-H880 ◽  
Author(s):  
T. Murohara ◽  
K. Kugiyama ◽  
M. Ohgushi ◽  
S. Sugiyama ◽  
H. Yasue
Keyword(s):  
Methylene Blue ◽  
Cigarette Smoke ◽  
Coronary Arteries ◽  
Cigarette Smoke Extract ◽  
Isometric Tension ◽  
Relaxing Factor ◽  
Prostaglandin F2 Alpha ◽  
Endothelium Derived Relaxing Factor ◽  
Pig Coronary Arteries

To test whether cigarette smoke extract (CSE) influences the endothelial regulation of vascular tone in vitro, pig coronary arterial rings were incubated in organ chambers and isometric tension changes were examined. CSE was prepared by bubbling mainstream smoke of one filter cigarette into phosphate-buffered saline (2 ml). Fresh CSE (3.3, 10, and 30 microliters/ml) elicited initial contraction and subsequent relaxation during stable contraction to prostaglandin F2 alpha (PGF2 alpha). Initial contraction to CSE was dependent on the presence of endothelium, whereas subsequent relaxation was endothelium independent. Initial contraction was significantly attenuated by superoxide dismutase (SOD), methylene blue, but not by catalase. Prior inhibition of the basal release of endothelium-derived relaxing factor by NG-monomethyl-L-arginine also inhibited the initial contraction, and this inhibition was reversed by coincubation with L-arginine but not D-arginine. Subsequent relaxation was significantly potentiated by SOD but was markedly attenuated by methylene blue. CSE reduced ferricytochrome c, and this reduction was significantly inhibited by SOD. In conclusion, CSE induced biphasic tension change, initial contraction, and subsequent relaxation during stable contraction to PGF2 alpha in isolated pig coronary arteries. The initial contraction may be, at least in part, mediated through the degradation of basally released endothelium-derived relaxing factor (nitric oxide) by superoxide anions derived from CSE.

scholarly journals EVALUATION OF IN-VITRO VASORELAXANT EFFECT (POTENTIAL ANTIHYPERTENSIVE) OF KIGELIA AFRICANA FRUIT METHANOL EXTRACT ON POTASSIUM CHLORIDE AND PHENYLEPHRINE INDUCED TENSION IN WISTAR RAT AORTA

2020 ◽  
Vol 4 (3) ◽  
pp. 470-475
Author(s):  
A. O. Isah ◽  
M. Idu ◽  
A. A. Abdulrahman ◽  
F. Amaechina
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Potassium Chloride ◽  
Methanol Extract ◽  
Muscle Relaxation ◽  
Rat Aorta ◽  
Smooth Muscle Relaxation ◽  
Organ Bath ◽  
Vasorelaxant Effect

This research on Kigelia africana was conducted in order to ascertain its ability to relax excited vascular smooth muscle in rat aorta. Preliminary investigation on whether the plant exhibits antihypertensive property was done before the evaluation of in vitro vasorelaxant effect. The vasorelaxant activity was determined using in vitro method on rat aorta with the aid of perfusion apparatus with a detachable organ bath. The administration of potassium chloride (KCl) raised the tension from 1.0 to 1.31 indicating that the aorta got to its peak of contraction. At 10 and 20mg/kg, the tension dropped significantly, showing relaxation of the smooth muscle while at 5mg/kg, drop in tension was insignificant at p˂0.05. However, at some of the doses, towards the end of experiment, there was steady resurge in tension showing that the aorta resumed contraction. On the application of phenylephrine (PE), the tension rose to 1.18g. On administration of the extract, the tension dropped slightly showing mild vascular smooth muscle relaxation. From the results obtained, there was seeming similarity in the action of the K. africana compared to amlodipine/Ramipril in KCl and PE induced tension in aorta respectively. However, at 10 and 20mg/kg, a substantial decrease in tension was noted indicating that the extract action is dose dependent. Thus, from this in-vitro smooth muscle relaxation study in rats, the methanol extract of K. africana has depressant property that was likely expressed by enhancing the closing of voltage operated calcium channel and ACE inhibiting activity in KCl and Phenylephrine induced tension respectively.

scholarly journals Effects of Aqueous Extract of Curcuma Longa Rhizome On Motility of Isolated Rabbit Jejunum

2019 ◽  
Vol 2 (1) ◽  
pp. 13-22
Author(s):  
B Umaru
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Aqueous Extract ◽  
Curcuma Longa ◽  
Muscle Relaxation ◽  
Soxhlet Extraction ◽  
Smooth Muscle Contraction ◽  
Smooth Muscle Relaxation ◽  
Rabbit Jejunum

Turmeric (curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family and the order Zingerberales. It is widely cultivated and used in the treatment of various ailments. In this study, the effect of aqueous extract of C. longa on isolated rabbit jejunum was investigated in vitro using Physiograph (Meditech, India). The rhizome of Curcumin was extracted using Soxhlet extraction method and distilled water was used as a solvent. The elemental analysis was determined using AAS and the result revealed the presence of Potassium, Magnesium, Iron and Nitrogen. The percentage concentrations of trace elements in the aqueous Curcumin rhizome were within the WHO standard limit. The aqueous extract at concentration tested (100 mg/ml) significantly decreased (p<0.05) jejunum smooth muscle contraction. Addition of Atropine (1mM) or Propranolol (1mM) further decreased the amplitude of jejunum smooth muscle contraction. Curcumin rhizome (100 mg/ml) blocked contraction induced by Ach (0.001μg/ml). The result of this work has shown that rhizome of C. longa produced jejunum smooth muscle relaxation, plant extract with antispasmodic activity may reduce gastrointestinal motility thereby delay gastric emptying and may be important in treatment of disease ailments like diarrhoea and colic.

Differential effects of nitrovasodilators and nitric oxide on porcine tracheal and bronchial muscle in vitro

1994 ◽  
Vol 77 (3) ◽  
pp. 1142-1147 ◽  
Author(s):  
K. Stuart-Smith ◽  
T. C. Bynoe ◽  
K. S. Lindeman ◽  
C. A. Hirshman
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Airway Smooth Muscle ◽  
Muscle Relaxation ◽  
Ringer Solution ◽  
Smooth Muscle Relaxation ◽  
Response Curves

Nitrovasodilators and nitric oxide relax airway smooth muscle. The mechanism by which nitrovasodilators are thought to act is by release of nitric oxide, but the importance of nitric oxide in nitrovasodilator-induced airway smooth muscle relaxation is unclear. The aim of this study was to compare the relaxing effects of nitric oxide itself with those of nitrovasodilators in porcine tracheal muscle and intrapulmonary airways and to investigate the mechanisms involved. Strips of porcine tracheal smooth muscle, rings of bronchi, and strips of bronchi from the same animal were suspended in organ chambers in modified Krebs Ringer solution (95% O2–5% CO2, 37 degrees C). Tissues were contracted with carbachol, and concentration-response curves to nitric oxide, sodium nitroprusside, and SIN-1 (an active metabolite of molsidomine) were obtained. All tissues relaxed to sodium nitroprusside, SIN-1, and nitric oxide. The relaxation to nitric oxide but not to SIN-1 or sodium nitroprusside was inhibited by methylene blue. Tissues pretreated with methylene blue that failed to relax to nitric oxide were, however, relaxed by sodium nitroprusside. These results demonstrate that nitrovasodilators relax airways by a mechanism other than by or in addition to the release of nitric oxide.

l-Glutamine in vitro regulates rat aortic glutamate content and modulates nitric oxide formation and contractility responses

2007 ◽  
Vol 293 (1) ◽  
pp. C142-C151 ◽  
Author(s):  
David Schachter
Keyword(s):  
Nitric Oxide ◽  
Amino Acids ◽  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Plasma Concentrations ◽  
Smooth Muscle Relaxation ◽  
No Formation ◽  
Ketoacid Dehydrogenase ◽  
Glutamate Synthesis

These studies test the hypothesis that l-glutamine at its physiological plasma concentration, ∼0.5 mM, can increase tissue content and net synthesis of glutamate in rat aortic segments in vitro, thereby mediating relaxation of the underlying smooth muscle in the elastic reservoir region of the thoracic aorta. Aortic segments were incubated in an isotonic medium with and without 21 amino acids at their normal plasma concentrations. Of these amino acids only l-glutamine and l-leucine at their plasma concentrations increased glutamate synthesis and content. Tissue glutamate content resulting from increasing concentrations of each precursor reached an upper level of ∼1.3–1.6 μmol/g wet wt. Regulation of the tissue glutamate content involves an interaction of the synthetic pathways in which l-glutamine inhibits the endothelial leucine-to-glutamate pathway. l-Glutamine increases nitric oxide (NO) formation, and NO inhibits the controlling enzyme of the endothelial leucine-to-glutamate pathway, the branched-chain α-ketoacid dehydrogenase complex. Treatment of precontracted aortic rings with 0.5 mM l-glutamine elicits smooth muscle relaxation, a response that requires endothelial nitric oxide synthase activity and an intact endothelium. The results demonstrate that in vitro l-glutamine at its normal concentration in plasma can regulate rat aortic glutamate content and modulate NO formation and contractility responses of the thoracic aortic wall.

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