Blockade of α2-Adrenergic Receptors in the Caudal Raphe Region Enhances the Renal Sympathetic Nerve Activity Response to Acute Intermittent Hypercapnia in Rats

Abstract

The study investigated the role of α2-adrenergic receptors of the caudal raphe region in the sympathetic and cardiovascular responses to the acute intermittent hypercapnia (AIHc). Urethane-anesthetized, vagotomized, mechanically ventilated Sprague-Dawley rats (n=38) were exposed to the AIHc protocol (5×3 min, 15 % CO2+50 % O2) in hyperoxic background (50 % O2). α2-adrenergic receptor antagonist-yohimbine was applied intravenously (1 mg/kg, n=9) or microinjected into the caudal raphe region (2 mM, n=12) prior to exposure to AIHc. Control groups of animals received saline intravenously (n=7) or into the caudal raphe region (n=10) prior to exposure to AIHc. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored before exposure to the AIHc protocol (T0), during five hypercapnic episodes (THc1-5) and at 15 min following the end of the last hypercapnic episode (T15). Following intravenous administration of yohimbine, RSNA was significantly greater during THc1-5 and at T15 than in the control group (P<0.05). When yohimbine was microinjected into the caudal raphe region, AIHc elicited greater increases in RSNA during THc1-5 when compared to the controls (THc1: 138.0±4.0 % vs. 123.7±4.8 %, P=0.032; THc2: 137.1±5.0 % vs. 124.1±4.5 %, P=0.071; THc3: 143.1±6.4 % vs. 122.0±4.8 %, P=0.020; THc4: 146.1±6.2 % vs. 120.7±5.7 %, P=0.007 and THc5: 143.2±7.7 % vs. 119.2±7.2 %, P=0.038). During THc1-5, significant decreases in HR from T0 were observed in all groups, while changes in MAP were observed in the group that received yohimbine intravenously. These findings suggest that blockade of the α2-adrenegic receptors in the caudal raphe region might have an important role in sympathetic responses to AIHc.

The Effects of Volatile Anesthetics on Renal Sympathetic and Phrenic Nerve Activity during Acute Intermittent Hypoxia in Rats

“…On the contrary, urethane does not seem to have a specific and predominant target for exerting its action and is preferentially used in experiments where the preservation of the reflexes is essential, as the observations closely mirror those made in conscious animals [53][54][55][56][57]. Previous reports indicate that both PNA and RSNA responses to chemoreflex activation may depend not only on the strength and type of the intermittent stimulus but also on the reoxygenation pattern [41,[58][59][60]. It has been demonstrated that hyperoxia has minimal effects on the magnitude of PNA response but can significantly attenuate the sympathetic response to acute airway obstruction in rats [59].…”

“…Next, the animals were placed in a prone position and fixed in a stereotaxic frame (Lab Standard; Stoelting Co., Wood Dale, IL, USA). A dorsal approach at the level of C5 nerve rootlet was used to access the right phrenic nerve, and the retroperitoneal approach was used to access the left renal sympathetic nerve, as previously described [23,41]. Each intact nerve was mounted on a silver wire electrode and covered with silicone gel to prevent it from drying and minimize noise artefacts.…”