RESUMEN
The heart rate response to isoproterenol (HR-Iso), density and affinity (kd) of beta-adrenergic (beta-AR) and muscarinic (M2) receptors were compared among three rodents with different generation-life histories of confinement and of high altitude exposure. The European guinea pig (Cavia porcellus) (EGp), a laboratory animal that arrived in Europe after the Spanish Conquest of South America and the Peruvian guinea pig (C. porcellus) (PGp), a semi-wild animal that came from the altiplano to sea level at least 25 generations ago, were used for intra-species comparison. Wistar rats (WR) were used for inter-species comparison as representative of a typical sea level laboratory animal. The HR-Iso was lower in EGp than in the PGp. The PGp showed the highest beta-AR density (P < 0.0005) and the highest beta-AR kd values (P < 0.0005) when compared to both EGp and WR groups (beta-AR Bmax (fmol mg-1 prot), WR, 19 +/- 4; Egp, 34 +/- 10; PGp, 74 +/- 15. beta-AR kd (pM), WR, 24 +/- 10; Egp, 17 +/- 7; PGp, 39 +/- 14). In contrast, PGp showed lower M2 receptor density values than the EGp (P < 0.0005). The WR had the highest M2 receptor densities (M2 Bmax (fmol mg-1 prot), WR, 188 +/- 15; Egp, 147 +/- 9; PGp, 118 +/- 6 and M2 kd (pM), WR, 65 +/- 12; Egp, 67 +/- 6; PGp, 92 +/- 2). The inter and intra-species differences found may be related to their respective history of confinement rather than to their history of exposure to high altitude.
Asunto(s)
Sistema Nervioso Autónomo/fisiología , Corazón/fisiología , Altitud , Animales , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Hipoxia/fisiopatología , Isoproterenol/farmacología , Ratas , Ratas Wistar , Receptores Adrenérgicos beta/metabolismo , Receptores Muscarínicos/metabolismoRESUMEN
We herein describe the regulation of cardiac receptors in a typical high-altitude native animal. Heart rate response to isoproterenol (HRIso) (beats.min-1.mg Iso.kg-1) and atropine, the density of beta-adrenergic (beta AR) and muscarinic (M2) receptors, and the ventricular content of norepinephrine (NE) and dopamine (DA) were studied in guinea pigs (Cavia porcellus). Animals native to Lima, Peru (150 m) were studied at sea level (SL) and after 5 wk at 4,300-m altitude (SL-HA). Animals native to Rancas [Pasco, Peru (4,300 m)] were studied at high altitude (HA) and after 5 wk at SL (HA-SL). HA animals had a lower HRIso, maximum number of beta AR binding sites (Bmax), beta AR dissociation constant (Kd), NE, and DA (P < 0.05) and a higher M2 Bmax (P < 0.001) when compared with the SL group. HA-SL showed an increase of the HRIso, beta Ar Kd, and NE (P < 0.05) and a decrease of the M2 Bmax and Kd (P < 0.0001) when compared with the HA group. The present study demonstrates the differential regulation and reversibility of the autonomic control in the guinea pig heart.
Asunto(s)
Altitud , Sistema Nervioso Autónomo/fisiopatología , Hipoxia/fisiopatología , Animales , Catecolaminas/metabolismo , Cobayas , Frecuencia Cardíaca/fisiología , Cinética , Miocardio/metabolismo , Sistema Nervioso Parasimpático/fisiopatología , Receptores Adrenérgicos beta/metabolismo , Receptores Muscarínicos/metabolismo , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
Heart rate (HR) response to isoproterenol (ISO) infusion (IP) is decreased in normal sea level (SL) natives exposed to high altitude (HA). Since norepinephrine plasma concentration is higher in HA hypoxia, a downregulation of beta-adrenoceptors (beta AR) was evoked. We explored this phenomenon at 3600 m in a HA normal population (HAN) and in polycythemic subjects (HAP). Results are compared to SL natives in normoxia (SLN), and during chronic hypoxia at 4800 m (SLH) (J Appl Physiol 65:1957-1961, 1988). ISO dose required to raise HR by 25 min-1 (I 25) is not different in HAN or HAP group when compared to SLN. Density of beta AR on lymphocytes was 39% and 25% lower in HAN and HAP than in SLN group, respectively. Chronotropic response to IP is similar in SL and HA subjects under their usual environmental conditions, while SL natives show a blunted response under hypoxia, probably due to a decrease in beta AR density. No adrenergic desensitization was found in highlanders. Lower beta AR density in HA groups could be an adaptive mechanism to chronic hypoxia. Polycythemia does not affect this responsiveness.