THE EFFECT OF ALPHA2-ADRENORECEPTORS ON RENAL SYMPATHETIC ACTIVITY DURING EXPOSURE TO ACUTE INTERMITTENT HYPOXIA IN RATS

Cilj istraživanja: Cilj ovog istraživanja je utvrditi učinak blokiranja alfa2-adrenoreceptora na aktivnost simpatičkog autonomnog sustava mjerenu promjenama aktivnosti renalnog živca pri izlaganju akutnim ponavljanim hipoksijama u štakora. Materijal i metode: Pokusi su izvedeni na 13 uretanom anesteziranih, vagotimiziranih i mehanički ventiliranih mužjaka štakora soja Sprague-Dawley, tjelesne mase 300-350 g. Simpatička aktivnost praćena je snimanjem lijevog renalnog živca. U pokusnoj skupini (N=7) životinjama je 10 minuta prije izlaganja AIH protokolu (5 x 3 min 9% O2) intravenski injiciran antagonist alfa2-adrenoreceptora johimbin (1 mg/kg). Analizirana je simpatička aktivnost i srednji arterijski tlak tijekom svih pet hipoksija (H1-H5), te 15 minuta (T15) nakon zadnje hipoksije. Promjena aktivnosti živca i vrijednosti tlaka uspoređene su s vrijednostima u bazalnim uvjetima prije izlaganja hipoksiji (T0). Kontrolnoj skupini (N=6) je umjesto johimbina intravenski injicirana ista količina fiziološke otopine te su životinje podvrgnute AIH protokolu. Rezultati: U kontrolnoj skupini tijekom AIH protokola dolazi do povećanja RSNA u H1 (142,34±38,46%; p=0,043) te značajnog smanjenja u H5 i T15 (61,46±32,39%; p=0,033; 61,88±33,66%; p=0,039) u odnosu na T0. U pokusnoj skupini značajno povećanje RSNA aktivnosti zabilježeno je samo u H1 (206,56±90,74%, p=0,021). RSNA aktivnost značajno se razlikuje između kontrolne i pokusne skupine u točkama H2, H3, H4 i H5 (p=0,022; p=0,010; p=0,010; p=0,010). Izlaganje akutnoj ponavljanoj hipoksiji dovodi do smanjenja srednjeg arterijskog tlaka u pokusnoj i kontrolnoj skupini u odnosu na bazalnu vrijednost (67,79±13,67% vs. 75,58±12,28%; p=0,195). Zaključci: Akutna ponavljana hipoksija dovodi do smanjenja simpatičke aktivnosti mjerene aktivnošću renalnog živca, dok intravenska primjena johimbina uzrokuje povećanje simpatičke aktivnosti prilikom izlaganja akutnoj ponavljanoj hipoksiji. Sistemska primjena otežava izvođenje zaključka o mjestu djelovanja johimbina obzirom na široku rasprostranjenost alfa2-adrenoreceptora unutar i izvan središnjeg živčanog sustava.Objectives and background: The aim of this research was to determine the effects of alpha2-adrenoreceptors blockade on sympathetic nervous system measured by changes in renal nerve activity during acute intermittent hypoxia in rats. Material and methods: Experiments were carried out on 13 urethane anesthetized, vagotomized and mechanically ventilated male Sprague-Dawley rats weighing 300-350 g. Sympathetic activity was monitored on the left renal nerve. Ten minutes prior to exposure to the AIH protocol (5 x 3 min 9% O2) alpha2-adrenergic antagonist yohimbine (1 mg/kg) was intravenously administered in the experimental group (N=7). During all 5 hypoxic events (H1-H5) of the AIH protocol and 15 minutes (T15) after the last hypoxia, sympathetic activity and mean arterial pressure were analyzed. Changes in the activity of the nerve and values of blood pressure were compared to the values of the baseline conditions before exposure to hypoxia (T0). The control group (N=6) received intravenous injection of the saline instead of yohimbine and underwent AIH protocol. Results: During AIH protocol the control group showed significant increase of RSNA activity in H1 (142.34±38.46%; p=0.043) and decrease in H5 and T15 (61.46±32.39%; p=0.033; 61.88±33.66%; p=0.039) compared to T0. In the experimental group, significant increase of RSNA activity was seen only in H1 (206.56±90.74%; p=0.021). RSNA activity was significantly different between the control and the experimental group in H2, H3, H4 and H5 (p=0.022; p=0.010; p=0.010; p=0.010). Exposure to acute intermittent hypoxia leads to decrease of mean arterial pressure in both experimental and control group compared to the baseline values (67.79±13.67% vs. 75.58±12.28%; p=0.195). Conclusions: Acute intermittent hypoxia leads to decreased sympathetic nerve activity measured by renal nerve activity, whereas intravenous administration of yohimbine evokes increase of sympathetic nerve activity during exposure to acute intermittent hypoxia. Systemic administration prevented us from drawing conclusions about precise site of action of yohimbine since alpha2-adrenoreceptors are dispersed throughout the central and peripheral nervous system