Excitatory Inputs from Carotid Bodies Drive Respiratory Changes in Renovascular Hypertensive Rats
Authors: Del Rosso de Melo Mariana , Gasparini Silvia , Silva Elaine Fernanda , Karlen‐Amarante Marlusa , Speretta Guilherme F.F. , Lauar Mariana Ruiz , Pedrino Gustavo , Menani Jose Vanderlei , Colombari Debora S.A. , Zoccal Daniel B , Colombari Eduardo 
Published: June 2021

The renin‐angiotensin system (RAS) and sympathetic overactivity are closely related with the development of hypertension. The renovascular hypertension is a model of secondary hypertension that is experimentally induced by two kidneys‐one clip (2K1C) surgery. Recently, studies have demonstrated that the carotid bodies (CB) contribute to the maintenance of hypertension in 2K1C rats. By the fact that respiratory activity is also affected by CB inputs, we sought to investigate the possible ventilatory changes in 2K1C hypertensive rats and the potential involvement of CB afferent activity on these changes. Silver clips were implanted around the left renal artery of male normotensive Holtzman rats (150 g) to induce renovascular hypertension. Six weeks later, hypertensive 2K1C rats (n=14) showed, in conscious state, elevated resting tidal volume (VT: 9.2 ± 0.6 ml.Kg−1) and minute ventilation VE (898 ± 61 ml.Kg−1.min−1) than normotensive/sham animals (n=12) (VT: 7.2 ± 0.3 ml.Kg−1, p<0.001), (VE: 629 ± 26 ml.Kg−1.min−1, p<0.001). During hypoxia (7% O2), hypertensive/sham rats exhibited an amplified hypoxic ventilatory response (Δ VE: 724 ± 91 vs. 380 ± 51 ml.Kg−1.min−1, p<0.001), due to larger increases in VT (Δ VT: 5 ± 0.8 vs 2.7 ± 0.6 ml.Kg−1; p<0.05) than normotensive/sham group. The hyperventilation of 2K1C rats were observed even in the presence of arterial alkalosis/urinary acidification and coexisted with augmented plasma renin activity and amplified hypoxic ventilatory response (p<0.05). Carotid body removal (CBR) two weeks before experiments (4th week after clipping) significantly reduced pulmonary ventilation in 2K1C rats (n=7) (5.3 ± 0.5 ml.kg−1, p<0.001) and VE (630 ± 73 ml.kg−1.min−1, p<0.001) compared to hypertensive/sham animals. CBR did not change the pulmonary ventilation in normotensive rats (n=7). Using the decerebrated, arterially perfused in situ preparations of juvenile normotensive rats (n=8), we verified that intra‐arterial administration of angiotensin II increased HN burst amplitude (Δ = 14.4 ± 5.9% from baseline), but did not modify PN burst amplitude and frequency (ΔPN amplitude: 3.1 ± 2.7% from baseline and ΔPN frequency: 9.8 ± 6.4% from baseline). On the other hand, in the CBR group, ANG II reduced PN and HN burst amplitude (ΔPN amplitude: −29.5 ± 5.6% and ΔHN amplitude: −15.1 ± 1.6% from baseline, p<0.05) and increased PN burst frequency (ΔPN frequency: 49.9 ± 16% from baseline). Our results indicate that angiotensin II‐dependent renovascular hypertensive rats exhibited resting hyperventilation by mechanisms that are dependent on carotid body afferent inputs.Support or Funding InformationFAPESP (2014/01159‐6; 2015/23467‐7), CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.