Vascular adaptation to exercise in humans: Role of hemodynamic stimuli

On the 400th anniversary of Harvey’s Lumleian lectures, this review focuses on “hemodynamic” forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century discovery that endothelial cells modify arterial tone via paracrine transduction provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the interrelationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions, and the implications for human health. Exercise modifies blood flow, luminal shear stress, arterial pressure, and tangential wall stress, all of which can transduce changes in arterial function, diameter, and wall thickness. There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute to the well-established decrease in cardiovascular risk attributed to physical activity. © 2017 the American Physiological Society

Environmental drivers of population-level variation in the migratory and diving ontogeny of an Arctic top predator

This work is an output of the ARISE project (NE/P006035/1 and NE/P00623X/1), part of the Changing Arctic Ocean programme jointly funded by the UKRI Natural Environment Research Council (NERC) and the German Federal Ministry of Education and Research (BMBF). Fieldwork in Canada was carried out under a Canadian Council on Animal Care permit no. NAFC2017–2 and funded by Fisheries and Oceans Canada and a bursary from Department for Business, Energy and Industrial Strategy (BEIS) administered by the NERC Arctic Office. Fieldwork in the Greenland Sea was approved by the Greenland Ministry of Fisheries, Hunting and Agriculture and the Norwegian Food Safety Authority (permit no. 11546) as part of the Northeast Greenland Environmental Study Program 2017–2018 (by the Danish Centre for Environment and Energy at Aarhus University, The Greenland Institute of Natural Resources and the Environmental Agency for Mineral Resource Activities of the Government of Greenland) and financed by oil licence holders in the area.The development of migratory strategies that enable juveniles to survive to sexual maturity is critical for species that exploit seasonal niches. For animals that forage via breath-hold diving, this requires a combination of both physiological and foraging skill development. Here, we assess how migratory and dive behaviour develop over the first year of life for a migratory Arctic top predator, the harp seal Pagophilus groenlandicus, tracked using animal-borne satellite relay data loggers. We reveal similarities in migratory movements and differences in diving behaviour between 38 juveniles tracked from the Greenland Sea and Northwest Atlantic breeding populations. In both regions, periods of resident and transitory behaviour during migration were associated with proxies for food availability: sea ice concentration and bathymetric depth. However, while ontogenetic development of dive behaviour was similar for both populations of juveniles over the first 25 days, after this time Greenland Sea animals performed shorter and shallower dives and were more closely associated with sea ice than Northwest Atlantic animals. Together, these results highlight the role of both intrinsic and extrinsic factors in shaping early life behaviour. Variation in the environmental conditions experienced during early life may shape how different populations respond to the rapid changes occurring in the Arctic ocean ecosystem.Publisher PDFPeer reviewe

Intermittent ATP release from nerve terminals elicits focal smooth muscle Ca2+ transients in mouse vas deferens

A confocal Ca(2+) imaging technique has been used to detect ATP release from individual sympathetic varicosities on the same nerve terminal branch. Varicose nerve terminals and smooth muscle cells in mouse vas deferens were loaded with the Ca(2+) indicator Oregon Green 488 BAPTA-1. Field (nerve) stimulation evoked discrete, focal increases in [Ca(2+)] in smooth muscle cells adjacent to identified varicosities. These focal increases in [Ca(2+)] have been termed ‘neuroeffector Ca(2+) transients’ (NCTs). NCTs were abolished by α,β-methylene ATP (1 μM), but not by nifedipine (1 μM) or prazosin (100 nm), suggesting that NCTs are generated by Ca(2+) influx through P2X receptors without a detectable contribution from L-type Ca(2+) channels or α(1)-adrenoceptor-mediated pathways. Action potential-evoked ATP release was highly intermittent (mean probability 0.019 ± 0.002; range 0.001-0.10) at 1 Hz stimulation, even though there was no failure of action potential propagation in the nerve terminals. Twenty-eight per cent of varicosities failed to release transmitter following more than 500 stimuli. Spontaneous ATP release was very infrequent (0.0014 Hz). No Ca(2+) transient attributable to noradrenaline release was detected even in response to 5 Hz stimulation. There was evidence of local noradrenaline release as the α(2)-adrenoceptor antagonist yohimbine increased the probability of occurrence of NCTs by 55 ± 21 % during trains of stimuli at 1 Hz. Frequency-dependent facilitation preferentially occurred at low probability release sites. The monitoring of NCTs now allows transmitter release to be detected simultaneously from each functional varicosity on an identified nerve terminal branch on an impulse-to-impulse basis

PREDICTORS OF HYPERTENSION

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74570/1/j.1749-6632.1978.tb25565.x.pd

Sry delivery to the adrenal medulla increases blood pressure and adrenal medullary tyrosine hydroxylase of normotensive WKY rats

BACKGROUND: Our laboratory has shown that a locus on the SHR Y chromosome increases blood pressure (BP) in the SHR rat and in WKY rats that had the SHR Y chromosome locus crossed into their genome (SHR/y rat). A potential candidate for this Y chromosome hypertension locus is Sry, a gene that encodes a transcription factor that is responsible for testes development and the Sry protein may affect other target genes. METHODS: The following study examined if exogenous Sry would elevate adrenal Th, adrenal catecholamines, plasma catecholamines and blood pressure. We delivered 10 μg of either the expression construct, Sry1/pcDNA 3.1, or control vector into the adrenal medulla of WKY rats by electroporation. Blood pressure was measured by the tail cuff technique and Th and catecholamines by HPLC with electrochemical detection. RESULTS: In the animals receiving Sry there were significant increases after 3 weeks in resting plasma NE (57%) and adrenal Th content (49%) compared to vector controls. BP was 30 mmHg higher in Sry injected animals (160 mmHg, p < .05) compared to vector controls (130 mmHg) after 2–3 weeks. Histological analysis showed that the electroporation procedure did not produce morphological damage. CONCLUSION: These results provide continued support that Sry is a candidate gene for hypertension. Also, these results are consistent with a role for Sry in increasing BP by directly or indirectly activating sympathetic nervous system activity

The Physiology of Vasodilatation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68237/2/10.1177_000331976101200602.pd

Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior

Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro