Proceedings of The Physiological Society

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC133

Poster Communications

Similarity and differences in action of high-energy photon and proton irradiation on vascular function in rats

A. I. Soloviev1, T. Novokhatska1, K. Klymenko1, I. Monchak1, A. Khromov1, N. Dobrelya1, O. Pavlova1, A. Valkov2, A. Piskarev2, P. Nolan3, P. Pusa3, A. Nahum4

1. Institute of Pharmacology and Toxicology, Kiev, Ukraine. 2. Institute for Nuclear Researches, Kiev, Ukraine. 3. Liverpool University, Liverpool, United Kingdom. 4. Clatterbridge Cancer Center, Clatterbridge, United Kingdom.

The patients with neoplasm receiving photon or hadrons therapy (PT/HT) can develop unwanted side cardio-vascular effects. Up to date there have been no studies that directly compare acute effects of PT and HT on vascular function. That is why comparison of these effects is the main goal of this study. Experimental design comprised outward macroscopic potassium currents (IKo) measurements provided in single rat aortic smooth muscle (SM) cells using whole-cell patch clamp technique, isolated aortic rings endothelium-dependent acetylcholine (Ach)-induced vascular relaxations (contractile recordings), Langendorff-perfused hearts and non-invasive systolic arterial blood pressure (BP) measurements. Photons were delivered using 60Co gamma-rays (0.8 Gy min-1,TGT ROCUS M). The particle irradiation was done using 60-MeV energy proton beam accelerated in the U-240 isochronous cyclotrone. Particle beam parameters were established on the basis of modeling data using semiimperical model of Ziegel, Biersack and Littmark (1985). We take into account the average values of the tissue density and element composition in the irradated arrea. Rats were exposed to a total absorbed dose of 6 Gy in both kinds of irradiation impact and then were euthanized on 9 day following the irradiation. Both PT and HT led to an increased SM sensitivity to alpha-agonist arterenol while amplitudes of Ach-induced relaxations had decreased. PT decreased the maximal Ach-induced relaxation (Rmax) on 9th day post-irradiation from 91±2% in a control to 80±3 vs 53±3% under HT (pD2 was 7.8±0.2 in a control, 7.0±0.02 and 6.9±0.04 under PT and HT, respectively, n=14, P<0.05). It is important to note that PT led to decrease in Rmax on the 30th day post-irradiation up to 51±3%, i.e. this value is close to that seen on 9th day after HT. After 9d IKo, which is mainly due to current through Maxi-K+ channels, from cells underwent PT and HT have been reduced from control 32±2 pA/pF to 18±1 pA/pF and to 10±1 pA/pF at +70 mV, respectively (n=7, p<0.05).The voltage-dependens of activation (V1/2) was shifted to more positive voltages and the activation kinetics were slower in the HT treated cells compared with PT and control. The HT was without significant effect on systolic BP in rats (128±8 mm Hg vs 122±8 mm Hg in a control) while PT produced significant hypertension development on the 9th day of post-irradiation (158± 6mm Hg vs 126±8 mm Hg in a control, n=7, p<0.05). Both HT and PT were without effect on cardiac contractility in Langendorff-perfused rat hearts. Thus, effects of PT and HT on vascular function are in substantially the same direction, except arterial blood pressure, but their intensity differs significantly. The data obtained provide new relevant information on the impact of the different radiation species on vascular tissues.

Where applicable, experiments conform with Society ethical requirements