PEMF and aorta stiffening

This post reviews Kavat 2009, a study showing that PEMF similar to that produced by many holistic medicine device can lessen like of responsiveness of aorta from rodents with a chemically induced form of diabetes. A device used to measure aorta stiffness in humans is also presented.

Brief summary of the Kavat 2009 PEMF study

Servet Kavat of Cukurova University, Adana, Turkey published a study in 2009 testing the hypothesis that PEMF could restore vascular tone in rats injected with streptozotocin, an alkylating agent that is particularly toxic to insulin producing pancreatic beta cells. The Kavat study is very much DM1, not type 2 diabetes.

Kavat 2009 used 50 Hz as the AC source to supply coils that generated 5 mT magnetic fields at the point of exposure. DM1 and control rats were exposed (or not) to PEMF four times daily for 30 min for the 30 day study.

DM1 made the resting membrane potential of the aorta rings less negative (polarized),and decreased response to agents inducing contraction and relaxation. PEMF partially restored response to agents inducing relaxation of the aorta rings.

Aorta What is stiffness ?

• Stiffness can be a constant k= Force / displacement. It is the opposite of compliance. If a pulse of blood is forced through an aorta that does not stretch out, the aorta is said to be stiff.
• Aorta stiffening may be a consequent of the aging process (Pierce 2022) and type 1 diabetes mellitus, DM1 . In both cases hypertension is a risk factor. (Brandts 2021)
• Stiffness of major vessels can lead to organ damage.

SphygmoCor PWV, measuring stiffness

Pulse wave velocity (PWV) is the time it takes a blood pressure pulse to travel a given distance in the circulatory system, i.e. the velocity. The gold standard distance given by Wikipedia authors is carotid to femoral.

The cost of the ground breaking SphygmoCor technology deserves closer examination. One must inquire on the website. Complementing the Kavat 2009 study, the Brandts 2021DM1 aorta stiffening study used nuclear magnetic resonance imaging (MRI) to measure aorta stiffness in their DM1 population study. The argument was that traditional sonography does not get into deep regions of the thoracic cavity. Brandts and authors give an excellent overview of the impact of DM1 on aorta stiffening in humans. Most relevant is the role of hypertension in this condition. With no further introduction, the next section explores the Kavak 2009 study as it relates to aorta

Kavak 2009 rat aorta rings and PEMF in depth

Must See image from Olchanheski 2018

These thoracic aorta strips were not denuded of endothelial cells. The neurotransmitter acetylcholine (ACh) interacts with receptors on endothelial cells that then cause smooth muscle cells to relax. Kavak 2009 noted prior research suggesting that DM1 diabetic hypertension was due to failure of smooth muscle to relax in response to signals coming from endothelial cells. Contraction was induced with phenylephrine (PE) which activates the α₁ adrenergic receptor. This heterotrimeric G protein coupled receptor fires through the Ca²⁺ mobilizing Gα_q subunit. When membrane potential was measured, it was via electrodes injected into the smooth muscle layer.

summary of results

• Table 1 The DM1 mice gained less weight in the later weeks and had higher blood glucose over the course of four weeks. Note that this predisposes the rats to advanced glycation end products, see the Pierce 2022 aorta stiffening post.
• Fig 1 Regardless of PEMF exposure, aortas from the DM rats were less responsive to PE, an agent that causes blood vessels to contract.
• Fig 2 compared relaxation of aorta rings from the four groups of rats to ACh and the nitric oxide donor SNP. The influence of ACh depends on the receptor it binds to: nitotinic or muscarinic. Muscarinic receptors mediate relaxation via a G-protein coupled cAMP pathway. The nicotinic receptor is a ligand gated ion channel that leads to contraction. Relaxation of the DM1 aorta rings in response to ACh was almost half that of the control. PEMF partially restored normal function. NO induced relaxation was less dependent on DM1 and prior PEMF treatment.
• Fig3 compared resting membrane potential and membrane potential after PE (contraction) and ACh / NO (relaxation). Resting membrane potential should be interior negative relative to the outside of the cell.. Adding PE causes the membrane potential to become more positive, ACh/SNP more negative. In all cases the DM1 aorta rings had membrane potentials less negative than their control counterparts.
• Fig4 The NO synthesis inhibitor L-NO-ARG was used in conjunction with the prostaglandin synthesis inhibitor indomethacin. L-NO-ARG and the combination produced a transient membrane hyper polarization in thoracic aorta rings from DM1 rats indicating that NO release probably played a role in the hyper polarization. PEMF made no difference. The well motivated reader may want to consult the Yang 2020 cartoon when viewing Fig 4 in Kavak 2009. PGE1 produced by corpus cavernosum endothelial cells increases cAMP in smooth muscle cells and phosphorylation of K⁺ channels by cAMP dependent protein kinase. Likewise, NO from endothelial cells activates the production of cGMP in smooth muscle cells landing to cGMP dependent protein kinase phosphorylation of K⁺ channels.
• Table 2 PKG phosphorylation Ca²⁺ gated K⁺ channels ion was addressed with channel inhibitors. Charybdotoxin is a protein inhibitor of single conductance Ca²⁺-activated K⁺ channels. Apamine is an inhibitor of small conductance Ca²⁺-activated K⁺ channels charybdotoxin and apamine produced a transient depolarization in all groups. UniProt’s PKG online annotation lists a variety of potential targets most of which tip the balance towards smooth muscle relaxation. Targets other than ion channels may be involved.

discussion and conclusions

“It is possible that exposure to PEMF increases intracellular Ca²⁺ in vascular endothelial cells followed by activation of protein kinase C followed by an increase in fibroblast growth factor (FGF-2) transcription. Activation of Ca²⁺ gated K⁺ channels are part of the model to explain increased relaxation in the DM1 aorta rings. ” It must be remembered that

1. The rats that the aorta were removed from were exposed to PEMF daily.
2. FGF-2, aka basic FGF, has a rather interesting write up by Wikipedia authors.
3. FGF2 binds to the fibroblast growth factor receptor 1 (FGFR1) FGFR1 is a receptor tyrosine kinase, a family of enzymes known for eliciting gene transcription in response to growth factors. A comment was made about bFGF being in the sub endotehlial extracellular matrix of blood vessels. bFGF may also translocate to the nucleus. UniProt bFGF annotation is consistent with Wikipedia.
4. Many of the FGFR1 downstream signaling events that probably numerous Wikipedia authors have contributed intersect Ca²⁺ signaling.

Kavat 2009 is a study that suggests long term vascular benefits of PEMF.

Conclusions

The featured Wikimedia Commons image is a 3D print of an abdominal aorta. It even looks like those flexible, expandable water hoses. Some water colors water hoses are also included. This is why we care about aorta stiffening. The Kavak 2009 study demonstrated that PEMF can influence response of aorta rings from rats with rats with chemically induced diabetes mellitus. Pierce 2022 outlined various causes of age related aorta stiffening. Most of these causes have been shown to benefit from one form of PEMF or another. The SphygmoCor has the potential to measure changes in vascular stiffness/compliance in response to PEMF.

References

• An DW, Muhammad IF, Li MX, Borné Y, Sheng CS, Persson M, Cai RZ, Guo QH, Wang JG, Engström G, Li Y, Nilsson PM. Carotid-Femoral Pulse Transit Time Variability Predicted Mortality and Improved Risk Stratification in the Elderly. Hypertension. 2021 Nov;78(5):1287-1295. free paper
• Brandts A, van Elderen SG, Tamsma JT, Smit JW, Kroft LJ, Lamb HJ, van der Meer RW, Westenberg JJ, de Roos A. The effect of hypertension on aortic pulse wave velocity in type-1 diabetes mellitus patients: assessment with MRI. Int J Cardiovasc Imaging. 2012 Mar;28(3):543-50. PMC free paper
• Kavak S, Emre M, Meral I, Unlugenc H, Pelit A, Demirkazik A. Repetitive 50 Hz pulsed electromagnetic field ameliorates the diabetes-induced impairments in the relaxation response of rat thoracic aorta rings. Int J Radiat Biol. 2009 Aug;85(8):672-9. Sci-Hub free paper