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1.
Intravenous (IV) infusions of neurotensin (NT) in anesthetized guinea pigs elicited dose-dependent pressor effects and tachycardia. Both effects were significantly reduced or abolished in guinea pigs given a chronic treatment with the neurotoxin capsaicin. In guinea pig isolated atria NT evoked a positive inotropic and chronotropic effect. Both effects were completely abolished in atria derived from capsaicin-treated guinea pigs. The positive inotropic and chronotropic effects of NT in guinea pig atria were mimicked by capsaicin and calcitonin gene-related peptide (CGRP). These results were interpreted as an indication that NT produces its cardiovascular effects in guinea pigs by activating capsaicin-sensitive sensory neurons. 相似文献
2.
McClure KJ Maher M Wu N Chaplan SR Eckert WA Lee DH Wickenden AD Hermann M Allison B Hawryluk N Breitenbucher JG Grice CA 《Bioorganic & medicinal chemistry letters》2011,21(18):5197-5201
The discovery of a series of novel, potent, and selective blockers of the cyclic nucleotide-modulated channel HCN1 is disclosed. Here we report an SAR study around a series of selective blockers of the HCN1 channel. Utilization of a high-throughput VIPR assay led to the identification of a novel series of 2,2-disubstituted indane derivatives, which had moderate selectivity and potency at HCN1. Optimization of this hit led to the identification of the potent, 1,1-disubstituted cyclohexane HCN1 blocker, 2-ethoxy-N-((1-(4-isopropylpiperazin-1-yl)cyclohexyl)methyl)benzamide. The work leading to the discovery of this compound is described herein. 相似文献
3.
Juan F. Aggio Jos C. de Freitas 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,146(4):653
By perfusing their branchial chambers with filtered seawater, we have developed a preparation that allows us to maintain the swimming crab Callinectes danae outside water without any major effects on its cardiac activity. This in turn allowed us to selectively stimulate chemoreceptors located in different body parts, and specifically to discriminate between the receptors located in the branchial chambers and those located in the oral region (mainly in the mouthparts, antennules and antennae). We show that a taurine solution can evoke bradycardia when applied to the oral region or to a combination of the oral region and the branchial chambers. Although the precise localization of the oral region receptors involved remains to be determined, ablation experiments show that the olfactory organs (i.e., the antennules) are not involved. Finally, we show that although stimulating the pereiopods has no effect on the animals' cardiac activity it causes the animals to move, putatively to try to grasp a piece of food, a reaction not evoked by stimulating the gills or the oral regions. Our results lend support to the idea that chemoreceptors located in different parts of the body play different functional roles in decapod crustaceans. 相似文献
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Electrocardiographic aspects of skin diving 总被引:1,自引:0,他引:1
A. Bonneau F. Friemel D. Lapierre 《European journal of applied physiology and occupational physiology》1989,58(5):487-493
Electrocardiographic (ECG) aspects of skin diving were monitored by means of continuous ECG recording in a pool 15 m deep. Ten regularly trained divers with different levels of experience divid a minimum of three consecutive times, holding their beath, reaching depths of 6 m, 9 m, and 12 or 15 m. The water temperature was 28 degrees C. During the ascending part of these dives, bradycardia was observed in all skin-divers. Minimal heart rate correlated negatively with the diver's experience (number of dives previously performed). In six divers cardiac arrhythmia was observed. Atrial arrhythmias were sometimes isolated occurrences, but more frequently they were multiple. Ventricular arrhythmias tended to be bigeminal. Apparently, forced expiration through the snorkel when surfacing precipitated these rhythmic disorders. 相似文献
7.
Nathan J. VanDusen Joshua W. Vincentz Beth A. Firulli Marthe J. Howard Michael Rubart Anthony B. Firulli 《Developmental biology》2014
The Periostin Cre (Postn-Cre) lineage includes endocardial and neural crest derived mesenchymal cells of the cardiac cushions, neural crest-derived components of the sympathetic and enteric nervous systems, and cardiac fibroblasts. In this study, we use the Postn-Cre transgenic allele to conditionally ablate Hand2 (H2CKO). We find that Postn-Cre H2CKOs die shortly after birth despite a lack of obvious cardiac structural defects. To ascertain the cause of death, we performed a detailed comparison of the Postn-Cre lineage and Hand2 expression at mid and late stages of embryonic development. Gene expression analyses demonstrate that Postn-Cre ablates Hand2 from the adrenal medulla as well as the sphenopalatine ganglia of the head. In both cases, Hand2 loss-of-function dramatically reduces expression of Dopamine Beta Hydroxylase (Dbh), a gene encoding a crucial catecholaminergic biosynthetic enzyme. Expression of the genes Tyrosine Hydroxylase (Th) and Phenylethanolamine N-methyltransferase (Pnmt), which also encode essential catecholaminergic enzymes, were severely reduced in postnatal adrenal glands. Electrocardiograms demonstrate that 3-day postnatal Postn-Cre H2CKO pups exhibit sinus bradycardia. In conjunction with the aforementioned gene expression analyses, these results strongly suggest that the observed postnatal lethality occurs due to a catecholamine deficiency and subsequent heart failure. 相似文献
8.
Noren SR Cuccurullo V Williams TM 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2004,174(2):139-147
Bradycardia is an important component of the dive response, yet little is known about this response in immature marine mammals. To determine if diving bradycardia improves with age, cardiac patterns from trained immature and mature bottlenose dolphins (Tursiops truncatus) were recorded during three conditions (stationary respiration, voluntary breath-hold, and shallow diving). Maximum (mean: 117±1 beats·min–1) and resting (mean: 101±5 beats·min–1) heart rate (HR) at the water surface were similar regardless of age. All dolphins lowered HR in response to apnea; mean steady state breath-hold HR was not correlated with age. However, the ability to reduce HR while diving improved with age. Minimum and mean steady state HR during diving were highest for calves. For example, 1.5–3.5-year-old calves had significantly higher mean steady state diving HR (51±1 beats·min–1) than 3.5–5.5-year-old juveniles (44±1 beats·min–1). As a result, older dolphins demonstrated greater overall reductions in HR during diving. Longitudinal studies concur; the ability to reduce HR improved as individual calves matured. Thus, although newly weaned calves as young as 1.7 years exhibit elements of cardiac control, the capacity to reduce HR while diving improves with maturation up to 3.5 years postpartum. Limited ability for bradycardia may partially explain the short dive durations observed for immature marine mammals.Abbreviations
ADL
aerobic dive limit
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cADL
calculated aerobic dive limit
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ECG
electrocardiogram
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HR
heart rate
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TDR
time–depth recorder
Communicated by L.C.-H. Wang 相似文献
9.
《Bioorganic & medicinal chemistry》2014,22(15):4246-4256
We report herein the synthesis and structure–activity relationships (SAR) of a series of benzyl ether compounds as an S1P1 receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P1 and S1P3 agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P1/S1P3 selectivity. These changes of the S1P1 and S1P3 agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P1 X-ray crystal structure and S1P3 homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P1/S1P3 selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats. 相似文献
10.
Deacon NL Arnould JP 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2009,179(3):287-295
The development of cardiac control in association with terrestrial respiration patterns was examined throughout the period
of maternal dependence in Australian fur seal pups. Resting eupnoic heart rate and respiration rate were significantly correlated
(r
2 = 0.49) and both decreased with age (P < 0.05 in both cases). From an early age (1 month), pups displayed terrestrial apnoeas (18.1 ± 0.5 s) accompanied by substantial
bradycardia (127 beats min−1, a 13% decrease from eupnoic HR). Terrestrial apnoea duration increased significantly with age reaching a mean of 41 s just
prior to weaning, slightly lower than the mean dive duration (52 s) previously recorded for pups of the same age. Correspondingly,
mean apnoic heart rate decreased with age to 74 beats min−1 just prior to weaning, representing a 25% decrease on eupnoic heart rate. Importantly, concomitant with the decrease in mean
apnoic heart rate with age, an increase in the control of bradycardia was evident with the variability in instantaneous apnoic
heart decreasing such that older pups were able to maintain a low steady heart rate for the duration of the apnoea. The changes
seen in these parameters are similar to those reported during postnatal development in elephant seals (Mirounga spp.) and harbour seals (Phoca vitulina), and are considered indicative of the development of cardiac control. These findings suggest a common strategy for the development
of bradycardia control in both otariid and phocid seals. 相似文献