Characterization of positive inotropic effect of colforsin dapropate hydrochloride, a water-soluble forskolin derivative, in isolated adult rat cardiomyocytes

1999 ◽  
Vol 77 (4) ◽  
pp. 225-234 ◽  
Author(s):  
Rikako Miyake ◽  
Hiroyuki Yoshida ◽  
Kouichi Tanonaka ◽  
Yuki Miyamoto ◽  
Hideharu Hayashi ◽  
...  
Keyword(s):  
Calcium Transient ◽  
Water Soluble ◽  
Inotropic Action ◽  
Shortening Velocity ◽  
Adult Rats ◽  
Camp Content ◽  
Rat Cardiomyocytes ◽  
Positive Inotropic Action ◽  
Time To Peak ◽  
Rate Of Increase

The present study was undertaken to characterize the positive inotropic action of colforsin dapropate hydrochloride (NKH477), a novel water-soluble forskolin derivative, on isolated cardiomyocytes of adult rats. Simultaneous measurements of cellular contraction and intracellular calcium concentration ([Ca2+]i) were carried out. The effects of isoprenaline and ouabain on these parameters were also determined for comparison. The contraction and maximum [Ca2+]i of NKH477-, isoprenaline-, or ouabain-treated cells were increased concentration dependently. Peak shortening of NKH477-treated cells was positively correlated with the shortening velocity and inversely with the time to peak shortening. Maximum, but not minimum, [Ca2+]i in NKH477-treated cells was correlated with the rate of increase in [Ca2+]i and inversely with the time to maximum [Ca2+]i. Similar results were obtained with isoprenaline. In contrast, ouabain increased both maximum and minimum [Ca2+]i. Treatment with either NKH477 or isoprenaline increased cellular cAMP content, but treatment with ouabain did not. These results suggest that the positive inotropic action of NKH477 is associated with an increase in [Ca2+]i and acceleration of its kinetics.Key words: adenylate cyclase, calcium transient, colforsin dapropate, isoprenaline, ouabain.

scholarly journals Peak force and maximal shortening velocity of soleus fibers after non-weight-bearing and resistance exercise

1997 ◽  
Vol 82 (1) ◽  
pp. 189-195 ◽  
Author(s):  
Jeffrey J. Widrick ◽  
Robert H. Fitts
Keyword(s):  
Resistance Exercise ◽  
Elevated Level ◽  
Fiber Diameter ◽  
Weight Bearing ◽  
Normal Weight ◽  
Peak Force ◽  
Type I ◽  
Shortening Velocity ◽  
Adult Rats ◽  
Cross Sectional

Widrick, Jeffrey J., and Robert H. Fitts. Peak force and maximal shortening velocity of soleus fibers after non-weight-bearing and resistance exercise. J. Appl. Physiol. 82(1): 189–195, 1997.—This study examined the effectiveness of resistance exercise as a countermeasure to non-weight-bearing-induced alterations in the absolute peak force, normalized peak force (force/fiber cross-sectional area), peak stiffness, and maximal shortening velocity ( V o) of single permeabilized type I soleus muscle fibers. Adult rats were subjected to one of the following treatments: normal weight bearing (WB), non-weight bearing (NWB), or NWB with exercise treatments (NWB+Ex). The hindlimbs of the NWB and NWB+Ex rats were suspended for 14 days via tail harnesses. Four times each day, the NWB+Ex rats were removed from suspension and performed 10 climbs (∼15 cm each) up a steep grid with a 500-g mass (∼1.5 times body mass) attached to their tail harness. NWB was associated with significant reductions in type I fiber diameter, absolute force, normalized force, and stiffness. Exercise treatments during NWB attenuated the decline in fiber diameter and absolute force by almost 60% while maintaining normalized force and stiffness at WB levels. Type I fiber V oincreased by 33% with NWB and remained at this elevated level despite the exercise treatments. We conclude that in comparison to intermittent weight bearing only (J. J. Widrick, J. J. Bangart, M. Karhanek, and R. H. Fitts. J. Appl. Physiol. 80: 981–987, 1996), resistance exercise was more effective in attenuating alterations in type I soleus fiber absolute force, normalized force, and stiffness but was less effective in restoring type I fiber V oto WB levels.

Hyperthyroid adult rat cardiomyocytes. I. Nucleotide content, beta- and alpha-adrenoreceptors, and cAMP production

1989 ◽  
Vol 257 (5) ◽  
pp. C948-C956 ◽  
Author(s):  
C. M. Hohl ◽  
S. Wetzel ◽  
R. H. Fertel ◽  
D. K. Wimsatt ◽  
G. P. Brierley ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Adenine Nucleotide ◽  
Phosphodiesterase Inhibitor ◽  
Cardiac Cells ◽  
Beta Agonist ◽  
Camp Production ◽  
Adult Rats ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Half Maximal Effective Concentration

Ventricular myocytes isolated from the hypertrophied hearts of thyrotoxic adult rats have an increase in mean protein content per myocyte (6.3 +/- 0.2 vs. 4.4 +/- 0.2 ng) compared with euthyroid cells. Viability and adenine nucleotide profiles are similar in both populations, but NAD content of the hyperthyroid myocytes is depressed (4.9 +/- 0.2 vs. 5.5 +/- 0.2 nmol/mg for controls) and UTP is higher (1.2 +/- 0.09 vs. 0.9 +/- 0.04 nmol/mg). Binding of (-)-[125I]iodocyanopindolol to intact hyperthyroid myocytes is increased by 42% compared with controls, with no change in the dissociation constant (Kd). This elevation in beta-receptor number is correlated to enhanced beta-agonist-induced adenosine 3',5'-cyclic monophosphate (cAMP) production. The half-maximal effective concentration (EC50) for the euthyroid isoproterenol dose-response curve is 2.14 x 10(-7) M but is decreased to 2.51 x 10(-8) M in hyperthyroid cardiac cells. Basal adenylate cyclase activity is apparently not affected by thyroid hormones, since basal cAMP levels for both groups are identical (5 pmol/mg) and both rise roughly twofold in the presence of a phosphodiesterase inhibitor. Forskolin-induced cAMP production and cAMP-specific phosphodiesterase activity are similar as well. In contrast to beta-adrenergic response, there are no significant differences in alpha 1-antagonist [3H]prazosin binding parameters between hyperthyroid and euthyroid cardiomyocytes.

Functional significance of compensatory overloaded rat fast muscle

1982 ◽  
Vol 52 (2) ◽  
pp. 473-478 ◽  
Author(s):  
R. R. Roy ◽  
I. D. Meadows ◽  
K. M. Baldwin ◽  
V. R. Edgerton
Keyword(s):  
Biochemical Properties ◽  
Slow Muscle ◽  
Repetitive Stimulation ◽  
Contractile Properties ◽  
Sectional Area ◽  
Shortening Velocity ◽  
Cross Sectional ◽  
Time To Peak ◽  
Isometric Twitch

Chronic overload of a skeletal muscle by removing its synergists produces hypertrophy and marked changes in its metabolic and biochemical properties. In this study alterations in the contractile properties of the plantaris 12–14 wk after bilateral removal of the soleus and gastrocnemius were investigated. In situ isometric and isotonic contractile properties of overloaded plantaris (OP), normal plantaris (NP), and normal soleus (NS) were tested at 33 +/- 1 degree C. Op were 97% heavier than NP and produced 43 and 46% higher twitch (Pt) and tetanic (Po) tensions. However, NP produced more tension per cross-sectional area than OP (mean 26.2 vs. 21.6 N/cm2; P less than 0.001). Isometric twitch time to peak tension (TPT) and half-relaxation time (1/2RT) were significantly longer in OP (mean 36.4 vs. 32.5 ms and 23.9 vs. 18.4 ms). Mean maximum shortening velocity (Vmax, mm/s per 1,000 sarcomeres) were 34.1 for NP and 18.1 for OP (P less than 0.001). The degree of conversion toward the Vmax of NS was 74% compared with only 19 and 14% for TPT and 1/2RT. OP produced a higher proportion of Po at a given stimulation frequency than NP and showed less fatigue than NP after repetitive stimulation. Chronic overload of the fast plantaris modified to varying degrees the contractile properties studied toward that resembling a slow muscle. Although the maximum tension of OP was markedly enhanced it was not in proportion to the increase in muscle mass.

GPER mediates estrogen cardioprotection against epinephrine-induced stress

2021 ◽  
Author(s):  
Lu Fu ◽  
Hongyuan Zhang ◽  
Jeremiah Ong’achwa Machuki ◽  
Tingting Zhang ◽  
Lin Han ◽  
...  
Keyword(s):  
Culture Supernatant ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Protective Role ◽  
Left Ventricular ◽  
Internal Diameter ◽  
High Dose ◽  
Adult Rats ◽  
Rat Cardiomyocytes ◽  
Lactate Dehydrogenase Release

Currently, there are no conventional treatments for stress-induced cardiomyopathy (SCM, also known as Takotsubo syndrome), and the existing therapies are not effective. The recently discovered G protein- coupled estrogen receptor (GPER) executes the rapid effects of estrogen (E2). In this study, we investigated the effects and mechanism of GPER on epinephrine (Epi)-induced cardiac stress. SCM was developed with a high dose of Epi in adult rats and human-induced pluripotent stem cells–derived cardiomyocytes(hiPSC-CMs). (1) GPER activation with agonist G1/ E2 prevented an increase in left ventricular internal diameter at end-systole, the decrease both in ejection fraction and cardiomyocyte shortening amplitude elicited by Epi. (2) G1/ E2 mitigated heart injury induced by Epi, as revealed by reduced plasma brain natriuretic peptide and lactate dehydrogenase release into culture supernatant. (3) G1/E2 prevented the raised phosphorylation and internalization of β2-adrenergic receptors（β2AR）. (4) Blocking Gαi abolished the cardiomyocyte contractile inhibition by Epi. G1/E2 downregulated Gαi activity of cardiomyocytes and further upregulated cyclic adenosine monophosphate concentration in culture supernatant treated with Epi. (5) G1/E2 rescued decreased Ca2+ amplitude and Ca2+ channel current (ICa-L) in rat cardiomyocytes. Notably, the above effects of E2 were blocked by the GPER antagonist, G15. In hiPSC-CM (which expressed GPER, β1AR and β2ARs), knockdown of GPER by siRNA abolished E2 effects on increasing ICa-L and action potential duration in the stress state. In conclusion, GPER played a protective role against SCM. Mechanistically, this effect was mediated by balancing the coupling of β2AR to the Gαs and Gαi signalling pathways.

Comparative analysis of ontogenic changes in renal and intestinal biotin transport in the rat

2003 ◽  
Vol 284 (4) ◽  
pp. F737-F742 ◽  
Author(s):  
Svetlana M. Nabokina ◽  
Veedamali S. Subramanian ◽  
Hamid M. Said
Keyword(s):  
Age Groups ◽  
Membrane Vesicles ◽  
Transport Processes ◽  
Water Soluble ◽  
Kidney Cortex ◽  
Intestinal Epithelial ◽  
Adult Rats ◽  
Intestinal Epithelia ◽  
Sodium Dependent ◽  
Uptake Process

Biotin, an essential water-soluble micronutrient, cannot be synthesized by mammals; rather, it is obtained from exogenous sources via uptake by intestinal epithelia. Renal epithelia reclaim the vitamin that is filtered in the glomeruli. Both epithelia take up biotin via the sodium-dependent multivitamin transporter (SMVT). Little is known about ontogenic regulation of the renal and intestinal biotin transport processes and about the mechanism(s) involved in any such regulation. In this study, we sought to examine and compare ontogenic aspects of the renal and intestinal biotin uptake processes using purified brush-border membrane vesicles (BBMV) isolated from the kidney cortex and jejunum of suckling and adult rats. Clear ontogenic changes were observed in the intestinal biotin uptake process, which were mediated via changes in V max and apparent K m. Parallel changes were also seen in protein, mRNA, and transcription rate of SMVT as indicated by results of Western blotting, RT-PCR, and nuclear run-on assays, respectively. In contrast, biotin uptake by renal BBMV did not show ontogenic changes; i.e., it was similar in suckling and adult rats. Also, the levels of SMVT protein and mRNA were similar in the kidneys of both age groups. These data show that biotin uptake by renal and intestinal epithelial cells responds differently to ontogenic regulation. In addition, the ontogenic changes observed in the intestinal biotin uptake process involve the entry step of the vitamin at the BBM and appear to be mediated via a transcriptional mechanism(s).

Downregulation of aquaporin-2 and -3 in aging kidney is independent of V2 vasopressin receptor

2000 ◽  
Vol 279 (1) ◽  
pp. F144-F152 ◽  
Author(s):  
L. Preisser ◽  
L. Teillet ◽  
S. Aliotti ◽  
R. Gobin ◽  
V. Berthonaud ◽  
...  
Keyword(s):  
Binding Sites ◽  
Collecting Duct ◽  
Urinary Volume ◽  
Adult Rats ◽  
Camp Content ◽  
Aquaporin 2 ◽  
Age Related ◽  
Medullary Collecting Duct ◽  
V2 Vasopressin Receptor ◽  
Aging Kidney

The mechanisms underlying age-related polyuria were investigated in 10- and 30-mo-old female WAG/Rij rats. Urinary volume and osmolality were 3.9 ± 0.3 ml/24 h and 2,511 ± 54 mosmol/kgH2O in adult rats and 12.8 ± 0.8 ml/24 h and 1,042 ± 44 mosmol/kgH2O in senescent animals. Vasopressin V2 receptor mRNA did not significantly differ between 10 and 30 mo, and [3H]vasopressin binding sites in membrane papilla were reduced by 30%. The cAMP content of the papilla was unchanged with age, whereas papillary osmolality was significantly lowered in senescent animals. The expression of aquaporin-1 (AQP1) and -4 was mostly unaltered from 10 to 30 mo. In contrast, aquaporin-2 (AQP2) and -3 (AQP3) expression was downregulated by 80 and 50%, respectively, and AQP2 was markedly redistributed into the intracellular compartment, in inner medulla of senescent animals, but not in renal cortex. These results indicate that age-related polyuria is associated with a downregulation of AQP2 and AQP3 expression in the medullary collecting duct, which is independent of vasopressin-mediated cAMP accumulation.

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