Positive inotropy due to lowering cyclic GMP is also mediated by increases in cyclic AMP in control and hypertrophic hearts

1998 ◽  
Vol 76 (6) ◽  
pp. 605-612 ◽  
Author(s):  
Karen L Naim ◽  
Prem Rabindranauth ◽  
Harvey R Weiss ◽  
James Tse ◽  
Richard J Leone, Jr. ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Current Model ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Heart Weight ◽  
Control Group ◽  
Inotropic Effects ◽  
Significant Change

The aim of the current study was to determine if lowering myocardial cyclic GMP by guanylate cyclase inhibition would add independently to the positive inotropic effects caused by raising cyclic AMP and if these effects are modified in left ventricular hypertrophy (LVH) produced by aortic valve plication. Isoproterenol (ISO) (0.1 mg·kg-1·min-1) was infused into a branch of the left anterior descending coronary artery of seven control and eight hypertrophy open-chest anesthetized dogs. After 10 min, simultaneous infusion of methylene blue (MB) (2 mg·kg-1·min-1) was initiated at the same site. Hypertrophy increased heart weight and heart weight / body weight ratio. While both drugs increased left ventricular dP/dtmax, no additional global effects were observed in either group. Changes in regional variables followed the same pattern in both groups, i.e., ISO produced an increase that was enhanced by the addition of MB. ISO increased segment shortening, with a significant change in the control group. ISO increased regional force in both groups. The addition of MB increased force above ISO levels, with a significant change in the LVH group. ISO increased regional minute work (g·mm·min-1) (control, 1779 ± 428 to 2541 ± 500; LVH, 1157 ± 253 to 1839 ± 404) and O2 consumption. MB further increased regional work (control, 2993 ± 952; LVH, 2416 ± 853) and O2 consumption. ISO raised cyclic AMP (pmoles·g-1) (control, 468 ± 41 to 580 ± 84; LVH, 445 ± 43 to 562 ± 71) and had no effect on cyclic GMP (pmoles·g-1) (control, baseline 3.27 ± 0.22, ISO 2.87 ± 0.23; LVH, baseline 6.84 ± 1.12, ISO 5.66 ± 0.54). The addition of MB lowered cyclic GMP (control, 2.41 ± 0.26; LVH, 3.68 ± 0.35), but also increased cyclic AMP (control, 1021 ± 121; LVH, 1107 ± 134). Similar results were observed in control hearts using a specific soluble guanylate cyclase inhibitor (ODQ) in terms of changes in local work, O2 consumption, and cyclic nucleotides. Thus, at least part of the positive inotropic response to lowering cyclic GMP was mediated by changes in cyclic AMP in the current model. This was true in both control and LVH animals, although baseline cyclic GMP levels were higher, and a larger reduction in cyclic GMP was observed with MB in the LVH group.Key words: guanylate cyclase, coronary blood flow, myocardial shortening, myocardial work, myocardial O2 consumption, dog.

Relationship between cGMP and myocardial O2 consumption is altered in T4-induced cardiac hypertrophy

1995 ◽  
Vol 268 (2) ◽  
pp. H686-H691 ◽  
Author(s):  
H. R. Weiss ◽  
E. Rodriguez ◽  
J. Tse
Keyword(s):  
Cardiac Hypertrophy ◽  
Guanylate Cyclase ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Cyclase Activity ◽  
Heart Weight ◽  
O2 Consumption ◽  
Guanylate Cyclase Activity ◽  
O2 Extraction ◽  
Myocardial O2 Consumption

We tested the hypothesis that increases in guanosine 3',5'-cyclic monophosphate (cGMP) would reduce myocardial O2 consumption and that thyroxine (T4)-induced (0.5 mg/kg for 16 days) cardiac hypertrophy would change this relationship. Anesthetized open-chest New Zealand White rabbits were divided into four groups: control vehicle (CV, n = 7), control nitroprusside (CN, n = 6), T4 vehicle (T4V, n = 8), and T4 nitroprusside (T4N, n = 8). Vehicle or sodium nitroprusside (10(-4) M) was topically applied to the left ventricular subepicardium for 15 min. Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to determine O2 consumption. Guanylate cyclase activity and cGMP were determined by radioimmunoassay. T4 increased the heart weight-to-body weight ratio from 2.7 +/- 0.1 to 3.4 +/- 0.2. Topical application of nitroprusside had no significant hemodynamic effects. Nitroprusside significantly increased myocardial cGMP in control hearts (CV = 4.1 +/- 0.3 to CN = 12.4 +/- 5.0 pmol/g) and T4 hearts (T4V = 3.9 +/- 0.3 to T4N = 5.2 +/- 0.4). The increase in the level of myocardial cGMP was significantly greater in CN (+202%) than in T4N (+33%). There were no significant differences in basal or total guanylate cyclase activity between control and T4 rabbits. Myocardial O2 consumption significantly declined in both groups during nitroprusside (10.8 +/- 1.4 for CV to 7.3 +/- 1.0 for CN (-32%) and 13.6 +/- 1.2 for T4V to 9.9 +/- 1.4 ml O2.min-1.100 g-1 for T4N (-27%).(ABSTRACT TRUNCATED AT 250 WORDS)

P0875INFLUENCE OF CHRONIC KIDNEY DISEASE AND LEFT VENTRICULAR HYPERTROPHY ON CHANGE IN FGF23 AND RENIN-ANGIOTENSIN-ALDOSTERONE-SYSTEM

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kohei Okamoto ◽  
Hideki Fujii ◽  
Shunsuke Goto ◽  
Keiji Kono ◽  
Kentaro Watanabe ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Body Weight ◽  
Mrna Expression ◽  
Ventricular Hypertrophy ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Heart Weight ◽  
Control Group ◽  
Body Weight Ratio ◽  
Related Factors

Abstract Background and Aims Left ventricular hypertrophy (LVH) is a clinically important risk factor for mortality and often observed in patients with chronic kidney disease (CKD). Serum FGF23 levels are elevated in CKD patients, and the relationship between elevated FGF23 and LVH has been reported in the previous studies. However, whether elevated FGF23 is a cause or result of LVH and whether FGF23 directly or indirectly affects LVH remain unclear. Therefore, we investigated changes in heart weight, CKD-mineral and bone disorder (MBD) parameters, including FGF23, and renin-angiotensin-aldosterone system (RAAS) related-factors in the setting of LVH and CKD using a mouse model. Method In the present study, twenty-four C57BL/6J mice were used and divided into 4 groups; control group (N=6), CKD group (N=6), LVH group (N=6), and LVH+CKD group (N=6). The mice in the CKD group underwent left 2/3 nephrectomy at 11 weeks of age and right nephrectomy at 12 weeks of age. Those in the LVH group underwent transverse aortic constriction (TAC) at 10 weeks of age. Those in the LVH+CKD group, TAC at 10 weeks of age, and left 2/3 nephrectomy at 11 weeks of age, and right nephrectomy at 12 weeks of age were performed. At 16 weeks of age, echocardiography was performed for all the mice, and they were sacrificed for blood and urine analysis, histopathological analysis and evaluating mRNA expressions of CKD-MBD- and RAAS-related factors in the heart. Results The systolic blood pressure was significantly higher in the LVH+CKD group and the CKD group than in the control group. The heart weight/body weight ratio in the LVH+CKD group was the highest, and that in the LVH was higher than that in the CKD group. Although serum creatinine and phosphate levels increased in CKD condition, those were comparable between the CKD and LVH+CKD groups. The urinary albumin excretion also increased in the CKD and LVH+CKD groups compared to the LVH and control groups. Serum FGF23 levels increased in the LVH and CKD group compared to the control group, and those in the LVH+CKD group were the highest among all the study groups. The cardiac mRNA expressions of FGF23, angiotensinogen (ANG), angiotensin type 1 receptor (AT1R), and angiotensin-converting enzyme (ACE) were also increased by induction of LVH and CKD, and those in the LVH+CKD group significantly increased compared to other groups. Heart weight/body weight ratio was significantly correlated with serum FGF23 levels and mRNA expression of FGF23, ANG, AT1R, ACE. In addition, significant correlations of serum FGF23 levels and cardiac mRNA expression of FGF23 with cardiac mRNA expressions of RAAS-related factors were observed. Conclusion Our results suggest that serum FGF23 levels and cardiac mRNA expression of FGF23 increase with the development of LVH and CKD and the changes is possibly enhanced through the colocalized activation of RAAS.

scholarly journals Regression of gestational diabetes induced cardiomegaly in offspring of diabetic rat

2009 ◽  
Vol 24 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Honório Sampaio Menezes ◽  
Cláudio Galeano Zettler ◽  
Alice Calone ◽  
Jackson Borges Corrêa ◽  
Carla Bartuscheck ◽  
...  
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Weight Ratio ◽  
Diabetic Rats ◽  
Heart Weight ◽  
Diabetic Rat ◽  
Control Group ◽  
Computer Assisted ◽  
Significant Difference ◽  
Levene Test

PURPOSE: To compare body weight and length, heart weight and length, heart-to-body weight ratio, glycemia, and morphometric cellular data of offspring of diabetic rats (ODR) and of normal rats (control). METHODS: Diabetes was induced in 3 pregnant Wistar rats, bearing 30 rats, on the 11th day after conception by intraperitoneal injection of 50 mg/kg of streptozotocin. Six normal pregnant Wistar rats, bearing 50 rats, made up the control group. Morphometric data were obtained using a scale for the weight, length, heart and body measurements. Morphometric cellular data were obtained by a computer assisted method applied to the measurements of myocytes. Statistical analysis utilized Student's t-test, ANOVA and Levene test. RESULTS: Control offspring had greater mean body weight and length than offspring of diabetic rats (p < 0.001). Heart weight and length and heart-to-body ratios of newborn rats differed between groups at birth (p < 0.001), but showed no difference at 21 days. Mean nuclei area and perimetric value of the myocytes decrees throughout the first 21 days of life (p < 0.01) in the diabetic group. CONCLUSIONS: Heart hypertrophy on the offspring of diabetic rats at birth was demonstrated by the significant difference between the groups. After the eleventh day, no difference was found, which confirmed regression of cardiomegaly. The significant difference between the first and the 21th day of life, for nuclei area feature, demonstrate regression of cardiac hypertrophy in the offspring of diabetic rats.

A study on the safety evaluation of buphrenorphine administered through an autoinjector compared with manual injection using haematological and biochemical variables in rats

2016 ◽  
Vol 36 (9) ◽  
pp. 901-909 ◽  
Author(s):  
D Sheela ◽  
R Vijayaraghavan ◽  
S Senthilkumar
Keyword(s):  
Body Weight ◽  
Research Work ◽  
Safety Evaluation ◽  
Weight Ratio ◽  
The Body ◽  
Control Group ◽  
Body Weight Ratio ◽  
Significant Difference ◽  
Manual Group ◽  
Significant Change

Buprenorphine drug cartridge was made for autoinjector device for use in emergency and critical situations to reduce the morbidity and mortality. Water-filled cartridges were prepared and buprenorphine was injected aseptically in the cartridge, to make 0.05 and 0.10 mg/mL. Rats were injected intraperitoneally, buprenorphine (0.3 and 0.6 mg/kg), repeatedly with the autoinjector and compared with manual injection (7 days and 14 days) using various haematological and biochemical parameters. No significant change was observed in the body weight, organ to body weight ratio and haematological variables in any of the experimental groups compared with the control group. Except serum urea and aspartate aminotransferase, no significant change was observed in glucose, cholesterol, triglycerides, bilirubin, protein, albumin, creatinine, uric acid, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase. The autoinjectors deliver the drugs with spray effect and force for faster absorption. In the present study, the autoinjector meant for intramuscular injection was injected intraperitoneally in rats, and the drug was delivered with force on the vital organs. No significant difference was observed in the autoinjector group compared to the manual group showing tolerability and safety of the buphrenorphine autoinjector. This study shows that buprenorphine autoinjector can be considered for further research work.

Cardiac vasculature and flow during pressure-overload hypertrophy

1986 ◽  
Vol 251 (5) ◽  
pp. H1031-H1037 ◽  
Author(s):  
E. A. Breisch ◽  
F. C. White ◽  
L. E. Nimmo ◽  
C. M. Bloor
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Capillary Density ◽  
Left Ventricular ◽  
Control Group ◽  
Cross Sectional ◽  
Ventricle Hypertrophy ◽  
Aortic Cuff

The effects of pressure-overload hypertrophy (H) on myocardial blood flow and microvasculature were studied in the porcine left ventricle. Hypertrophy was produced in nine adult pigs by an aortic cuff constriction of the ascending aorta. Eight pigs served as controls. After 30 days the aortic cuff was released, and the hypertrophy group was studied 1 day postrelease. The degree of hypertrophy, determined by left ventricular-to-body weight ratio, was 45%. With hypertrophy, left ventricular blood flows were normal at rest. During exercise with adenosine infusion, myocardial blood flow to the endomyocardium was reduced compared with the control (C) group (H = 4.02 +/- 0.35, P less than 0.05; C = 5.33 +/- 0.41 ml X min-1 X g-1). Minimal coronary vascular resistance in the endomyocardium was increased during exercise with adenosine in the hypertrophy group compared with the control group. Anatomic studies revealed that hypertrophy causes a reduction in the endomyocardial capillary density (H = 1,654 +/- 168, P less than 0.025; C = 2,168 +/- 106, no./mm2) with a similar trend noted for the transmural arteriolar density. Arteriolar media wall cross-sectional area was unaffected by the pressure overload. These results indicate that changes in the vascular bed do not parallel myocyte growth during pressure-overload hypertrophy. The resultant anatomic imbalance compromises endomyocardial flow, making this region vulnerable to ischemia.

Antihyperlipidemic and Antiobesity potential of Aquilaria agallocha & Borago officinalis in Fixed Dose Combination; A Contingent Probe with Atorvastatin & Orlistat

2021 ◽  
Vol 17 ◽  
Author(s):  
Rohima Oraon ◽  
Tarique Mahmood ◽  
Arshiya Shamim ◽  
Farogh Ahsan ◽  
Mohammad Shariq ◽  
...  
Keyword(s):  
Weight Ratio ◽  
Good Control ◽  
Fixed Dose Combination ◽  
Atherogenic Index ◽  
Heart Weight ◽  
Fixed Dose ◽  
Control Group ◽  
High Dose ◽  
Borago Officinalis ◽  
Dose Combination

: Hyperlipidemia and Obesity have been an alarmingly rising health disorders for the past few decades worldwide. They eventually pave way for cardiovascular and other metabolic health risks that are manifested with elevated blood lipid levels. Atherosclerosis, Coronary artery disease and Cerebrovascular diseases, are some major complications of hyperlipidemia. The current clinically available drugs like, Statins & HMG-Co-A inhibitors have a good control on hyperlipidemia but present many insalubrious effects like myopathy & hepatotoxicity that questions their risk-benefit ratio. The current study was designed to develop a fixed-dose combination (FDC) of extracts of Aquilaria agallocha and Borago officinalis, to delve into therapeutic resources that have synergistic benefits and could overpower the adverse effects of modern therapy. These plants are well reported for cardioprotective, immunomodulatory and hepatoprotective potentials. The FDC developed with these plants was examined for its antihyperlipidemic and antiobesity potential in HFD fed animal model (Vijaya et al) for Hyperlipidemia. The extracts from leaves of Borago officinalis and Aquilaria agallocha were administered perorally for 28 days in a fixed dose combination (FDC) in HFD fed rats. The physical and the biochemical parameters; viz, the gross examination of liver, heart, heart weight/body weight ratio, atherogenic index, various hepatic & cardiac biomarker enzymes and serum lipid markers were scrutinized. The result of the study suggested that both the low and high dose of the FDC of Aquilaria agallocha & Borago officinalis has significant Anti-Hyperlipidemic and Anti-Obesity potential against High-fat diet-induced Hyperlipidemia and Obesity when compared to disease control group (at p<0.01 & p<0.001) and their effects were at par with clinically established drugs Atorvastatin & Orlistat.

Abstract P112: Estradiol Induces Physiological Hypertrophic Growth in the Healthy Mouse Heart

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Georgios Kararigas ◽  
Ba Tiep Nguyen ◽  
Hubertus Jarry ◽  
Vera Regitz-Zagrosek
Keyword(s):  
Weight Ratio ◽  
Treated Group ◽  
Left Ventricular ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Mouse Heart ◽  
Cross Sectional ◽  
Hypertrophic Growth ◽  
Protein Levels ◽  
Cycle Regulation

Estradiol-17beta (E2) has been shown to exert anti-hypertrophic actions by either attenuating or blunting the development of left ventricular hypertrophy. However, the vast majority of these studies have been performed in stressed or diseased hearts. Consequently, very little is known about the actions of E2 in the stress- and disease-free heart. The aim of our study was to identify and characterize structurally and molecularly the role of E2 in the healthy heart. Female C57Bl/6J mice were ovariectomized at the age of two months. Mice were randomly assigned into groups feeding on either an E2-containing (n = 19) or soy-free (Ctrl; n = 19) diet for three months. Following this, all mice were sacrificed and hearts were collected for weight measurement. Left ventricles were analyzed structurally by immunohistochemistry and molecularly by genome-wide expression profiling. E2 led to an increase in the heart weight (11%; P < 0.001) and the heart-to-body weight ratio (32%; P < 0.001) compared to Ctrl mice. Cardiomyocyte cross-sectional area revealed cardiomyocyte hypertrophy in E2 (n = 6) compared to Ctrl (n = 5) mice (32%; P = 0.004). Analysis of the left ventricular transcriptome identified 1059 probe sets (adjusted P ≤ 0.05) differentially expressed between E2 (n = 5) and Ctrl (n = 5). Hypergeometric testing for Gene Ontology showed most genes to be associated with cell cycle, regulation of growth, cell and tissue development. Pathway analysis revealed 140 pathways (adjusted P = 0.05) modulated between the two groups, such as the DNA replication and Wnt signaling pathways. Next, we tested the hypothesis that this hypertrophic effect of E2 is of the physiological type. To this extent, we identified that angiogenesis was increased with cardiac growth as determined by the microarray analysis and VEGF-A protein levels assessed by Western blotting. Furthermore, the embryonic gene program was not activated and no fibrosis was observed in the E2-treated group. In conclusion, our study is the first to demonstrate pro-hypertrophic actions of E2 in the healthy heart through the modulation of growth-related genes and pathways. Due to that we have characterized the hypertrophic effect of E2 as physiological, we expect this effect to be beneficial for the heart.

Abstract 152: Mitochondrial Fission Inhibitor Mdivi-1 Attenuates Angiotensin II-Induced Cardiovascular Remodeling

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Steven J Forrester ◽  
Tatsuo Kawai ◽  
Katherine J Elliott ◽  
Kunie Eguchi ◽  
Victor Rizzo ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Er Stress ◽  
Mitochondrial Fission ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Heart Weight ◽  
Cardiovascular Remodeling ◽  
Target Organs ◽  
Quantity Control ◽  
Affect Heart Rate

Mitochondrial dysfunction has been implicated in various types of cardiovascular diseases which may involve overload and de-compensation in mitochondrial quality/quantity control. However, limited mechanistic insight is available regarding the contribution and mechanism of mitochondrial quality control in hypertension. In the present study, we tested our hypothesis that enhancement of mitochondrial fission in vascular cells is involved in hypertensive vascular remodeling. 8 week old male C57/Bl6 mice were infused with angiotensin II (1000 ng/kg/min) for 2 weeks with or without treatment of mitochondrial fission inhibitor Mdivi-1 (25 mg/kg ip every other day). Mdivi-1 significantly inhibited AngII-induced left ventricular hypertrophy assessed by heart weight body weight ratio as well as by echocardiogram. Histological assessment of the Mdivi-1-treated mouse hearts further demonstrated significant suppression of vessel hypertrophy and fibrosis induced by AngII. However, Mdivi-1 did not affect heart rate or hypertension induced by AngII assessed by telemetry. KDEL and VCAM1 staining of the heart and aorta suggest attenuation of vascular ER stress and inflammation, respectively. In cultured rat vascular smooth muscle cell (VSMCs), AngII induced mitochondrial fission promoting Drp1 phosphorylation at Ser616 and Ser637. Pretreatment of Mdivi-1 (5 microM 30 min) attenuated 100 nM AngII-induced mitochondrial fission in VSMCs assessed by mito-tracker staining. Mdivi-1 also attenuated extracellular collagen accumulation induced by AngII in VSMCs assessed by Sirius Red staining quantification kit. In conclusion, this data suggests that Mdivi-1 treatment prevents AngII-induced cardiovascular remodeling independently of hypertension via suppression of mitochondrial fission and attenuation of ER stress and inflammation in target organs.

Simple fluctuation of Ca2+ elicits the complex circadian dynamics of cyclic AMP and cyclic GMP in Paramecium

1999 ◽  
Vol 112 (2) ◽  
pp. 201-207 ◽  
Author(s):  
K. Hasegawa ◽  
H. Kikuchi ◽  
S. Ishizaki ◽  
A. Tamura ◽  
Y. Tsukahara ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Concentration Camp ◽  
Dark Cycle ◽  
Camp Concentration ◽  
Mathematical Functions ◽  
Camp And Cgmp ◽  
Different Levels

The circadian dynamics of cyclic adenosine 3′,5′-monophosphate (cAMP) and cyclic guanosine 3′,5′-monophosphate (cGMP) were simulated in Paramecium multimicronucleatum. The mathematical functions determined closely mimic the Ca2+ dependence of adenylate cyclase (AC) and guanylate cyclase (GC) activities as documented in P. tetraurelia. Patterns of cAMP concentration ([cAMP]), cGMP concentration ([cGMP]), and the ratio [cGMP]/[cAMP] were calculated with respect to Ca2+ concentrations ([Ca2+]) fluctuating sinusoidally with a period of 24 hours at three different levels: low, medium, and high. The functions displayed varying patterns of [cAMP] characteristic for [Ca2+] fluctuating at each level, while patterns of [cGMP] and [cGMP]/[cAMP] almost paralleled [Ca2+] fluctuations. Similar patterns were observed for actual [cAMP] and [cGMP] measured during the light/dark cycle in P. multimicronucleatum, grown in axenic media additionally containing [Ca2+] at 25 (low), 100 (medium), or 400 (high) microM, respectively. The coincidence between simulated and measured fluctuations of [cAMP] and [cGMP] suggests that the circadian fluctuations of intracellular [Ca2+] primarily stimulate activities of AC and GC via their different degrees of Ca2+ dependence, which are ultimately responsible for the circadian spatiotemporal organization of various physiological functions in Paramecium.

Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck

1979 ◽  
Vol 237 (5) ◽  
pp. C200-C204 ◽  
Author(s):  
D. J. Stewart ◽  
J. Sax ◽  
R. Funk ◽  
A. K. Sen
Keyword(s):  
Cyclic Amp ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Salt Gland ◽  
Domestic Ducks ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.

Sign in / Sign up

Export Citation Format

Share Document