The two kidney-one clip (2K1C) renovascular hypertension depends on the renin-angiotensin system and sympathetic overactivity. The maintenance of 2K1C hypertension also depends on inputs from the carotid bodies (CB), which when activated stimulate the respiratory activity. In the present study, we investigated the importance of CB afferent activity for the ventilatory responses in 2K1C hypertensive rats and for phrenic and hypoglossal activities in in situ preparations of normotensive rats treated with angiotensin II. Silver clips were implanted around the left renal artery of male Holtzman rats (150 g) to induce renovascular hypertension. Six weeks after clipping, hypertensive 2K1C rats showed, in conscious state, elevated resting tidal volume and minute ventilation compared with the normotensive group. 2K1C rats also presented arterial alkalosis, urinary acidification, and amplified hypoxic ventilatory response. Carotid body removal (CBR), 2 wk before the experiments (4th week after clipping), significantly reduced arterial pressure and pulmonary ventilation in 2K1C rats but not in normotensive rats. Intra-arterial administration of angiotensin II in the in situ preparation of normotensive rats increased phrenic and hypoglossal activities, responses that were also reduced after CBR. Results show that renovascular hypertensive rats exhibit increased resting ventilation that depends on CB inputs. Similarly, angiotensin II increases phrenic and hypoglossal activities in in situ preparations of normotensive rats, responses that also depend on CB inputs. Results suggest that mechanisms that depend on CB inputs in renovascular hypertensive rats or during angiotensin II administration in normotensive animals increase respiratory drive.

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The mechanisms by which changes in intracranial pressure (ICP) occur during hypertension are unclear. The experimental 2K1C (2-kidney, 1-clip) hypertension is a model characterized by sympathetic and renin-angiotensin system overactivation in which ICP still needs investigation. In the present study, we analyzed ICP alterations during the development of 2K1C hypertension using invasive and noninvasive ICP recording methods. We also tested the importance of AT1R (angiotensin II type 1 receptor) activation for the ICP changes and investigated the integrity of the blood-brain barrier within central cardioregulatory nuclei in 2K1C hypertensive rats. 2K1C hypertension was induced in 6-week-old male rats (150 g). In the fourth week of 2K1C hypertension induction, when mean arterial pressure reached 162±2 mm Hg, ICP significantly increased, ICP pulse waveforms changed, increasing the ratio between the two peaks (P2/P1 ratio) of the ICP waveform. In the third week of 2K1C hypertension induction, blood-brain barrier disruption was detected within the hypothalamic paraventricular nucleus, rostral ventrolateral medulla, and nucleus tractus solitarius. In the sixth week, intravenous losartan (AT1R antagonist) or the vasodilator hydralazine acutely reduced arterial pressure to normotensive levels. Losartan, but not hydralazine, partially reduced the increase of ICP and P2/P1 ratio in hypertensive rats. These results show significant changes in ICP in 2K1C hypertensive rats and suggest that AT1R activation may contribute to elevated ICP during hypertension—an effect possibly intensified by the blood-brain barrier disruption in important central cardioregulatory nuclei in renovascular hypertensive animals.

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