Exposure to a moderate intensity static magnetic field enhances the hypotensive effect of a calcium channel blocker in spontaneously hypertensive rats

Abstract

We investigated the combined effects of a moderate intensity static magnetic field (SMF) and an L-type voltage-gated Ca(2+) channel blocker, nicardipine in stroke-resistant spontaneously hypertensive rats during the development of hypertension. Five-week-old male rats were exposed to SMF intensity up to 180 mT (B(max)) with a peak spatial gradient of 133 mT/mm for 14 weeks. Four experimental groups of 14 animals each were examined: (1) sham exposure with intraperitoneal (ip) saline injection (control); (2) SMF exposure with ip saline injection (SMF); (3) sham exposure with ip nicardipine injection (NIC); (4) SMF exposure with ip nicardipine injection (SMF + NIC). A disc-shaped permanent magnet or a dummy magnet was implanted in the vicinity adjacent to the left carotid sinus baroreceptor region in the neck of each rat. Nicardipine (2 mg/kg ip) was administered three times a week for 14 weeks, and then 15 min after each injection, arterial blood pressure (BP), heart rate (HR), baroreflex sensitivity (BRS), skin blood flow (SBF), skin blood velocity (SBV), plasma nitric oxide (NO) metabolites (NO(x) = NO(2) (-) + NO(3) (-)), plasma catecholamine levels and behavioral parameters of a functional observational battery were monitored. The action of nicardipine significantly decreased BP, and increased HR, SBF, SBV, plasma epinephrine and norepinephrine in the NIC group compared with the control respective age-matched group without changing plasma NO(x) levels. Neck exposure to SMF alone for 5-8 weeks significantly suppressed or retarded the development of hypertension together with increased BRS in SMF group. Furthermore, the exposure to SMF for 1-8 weeks significantly promoted the nicardipine-induced BP decrease in the SMF + NIC group compared with the respective NIC group. Moreover, the SMF induced a significant increase in plasma NO(x) in the nicardipine-induced hypotension. There were no significant differences in any of the physiological or behavioral parameters measured between the SMF + NIC and the NIC groups, nor between the SMF and the control groups. These results suggest that the SMF may enhance nicardipine-induced hypotension by more effectively antagonizing the Ca(2+) influx through the Ca(2+) channels compared with the NIC treatment alone. Furthermore, the enhanced antihypertensive effects of the SMF on the nicardipine-treated group appear to be partially related to the increased NO(x). Theoretical considerations suggest that the applied SMF (B(max) 40 mT, 0 Hz) can be converted into a changing magnetic field (B(max) 30-40 mT, 5.7-6.5 Hz or 7.5-8.3 Hz) in the baroreceptor region by means of the carotid artery pulsation. Therefore, we propose that the moderate intensity changing magnetic field, i.e., the magnetic field modulated by the pulse rate, may influence the activity of baroreceptor and baroreflex function.

Baroreceptor stimulation enhanced nitric oxide vasodilator responsiveness, a new aspect of baroreflex physiology

“…Importantly, baroreflex -NO interplay was confirmed in chronic experiments, where sinocarotid baroreceptor SMF exposure decreased blood pressure and evoked an increase in BRS and plasma NO metabolites (Okano and Ohkubo, 2005). A specific inhibitory effect of sympathetic activation on shear-mediated NO release (Hijmering et al, 2002) supplies additional argument for baroreflex-mediated sympathetic activity withdrawal based NO-sensitizing vasodilator mechanism.…”

Effects of Static Magnetic Fields on Blood Pressure in Animals and Humans

“…The above findings were partially elucidated when SHR were exposed to a 180 mT SMF (a magnet was implanted in the neck) for up to 14 weeks [66]. The SMF enhanced the hypotensive effect of nicardipine and caused a further increase in NO x during the 6th week of exposure compared with rats that also received nicardipine but were exposed to a sham SMF (control).…”

“…In a series of our later experiments [60][61][62][63][64][65][66][67], the previous works on the SMF effects on cutaneous microvasculature and microcirculation in conscious animals were extended. These studies focused on BP changes associated with SMF exposure.…”

“…Moreover, exposure to a 180 mT SMF for 5-8 weeks significantly suppressed or delayed the development of hypertension together with increased BRS in SHR [66]. Furthermore, it is postulated through theoretical calculations that the applied SMF can be converted into a changing magnetic field in the baroreceptor region by means of the carotid artery pulsation [66].…”

“…In summary, significant or nonsignificant arterial BP responses to moderate intensity SMF in mT level fields have been recently reviewed in experimental animals and/or humans: SMF exposures between 1 mT and 400 mT for anywhere between 10 min and 8 weeks (e.g., antihypertensive period for young SHR) could affect arterial BP, cutaneous microcirculation and/or hemodynamics [50,[52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][77][78][79][80]. The present review is a more up-to-date summary of the research in the relevant areas.…”