Hiroshi Hosomi

Neural control of urinary sodium excretion during hypertonic NaCl load in conscious rabbits: role of renal and hepatic nerves and baroreceptors

We examined responses of renal nerve activity, urine flow, and urinary Na+ excretion to a hypertonic NaCl infusion in chronically instrumented conscious rabbits with unilateral renal denervation. The intravenous infusion of 20% NaCl, at 0.2 ml/min for 30 min, increased plasma osmolality by 27 +/- 5 mOsm/kg, and plasma Na+ by 16 +/- 3 mEq/l, and decreased hematocrit by 5 +/- 1%. These changes were accompanied by a marked decrease in renal nerve activity by 82 + 7%. Urine flow and urinary Na+ excretion increased gradually and peaked at the end of infusion. The innervated kidney excreted 23.3 +/- 3.3 ml urine and 5.5 +/- 0.7 mEq Na+ for the subsequent 60 min. However, the contralateral denervated kidney excreted only 9.5 +/- 2.0 ml urine and 2.2 +/- 0.6 mEq Na+; these values were significantly less than those of the innervated kidney. To examine the role of the sinoaortic and cardiopulmonary baroreceptors and the hepatic nerves in the response of renal nerve activity to the hypertonic NaCl infusion, renal nerve activity was examined in conscious rabbits with sinoaortic baroreceptor denervation (SAD) plus vagotomy and/or section of the anterior and posterior hepatic nerves (SAPH). In rabbits with SAD plus vagotomy or SAPH, the NaCl infusion also decreased renal nerve activity. After combining SAPH and SAD plus vagotomy, the decrease in renal nerve activity was completely blocked. These results indicate that hypertonic NaCl infusion elicits a marked decrease in renal nerve activity which is mediated predominantly by sinoaortic and cardiopulmonary baroreflexes and the hepatic nerves, and that the decrease in renal nerve activity plays an important role in the augmentation of renal function.

Effect of pentobarbital anesthesia on renal sympathetic nerve activity in the rabbit

The effects of pentobarbital (PB) anesthesia on arterial pressure, heart rate, and renal nerve activity (RNA) were studied in chronically instrumented intact rabbits and rabbits with sinoaortic baroreceptor denervation (SAD). In intact rabbits, PB caused an initial decrease in mean arterial pressure from 82 +/- 2 to 42 +/- 5 mm Hg, which then returned to the control level within 5 min. RNA increased by 144 +/- 19% in response to hypotension induced by PB then also returned to the control level within 5 min. Heart rate increased by 56 +/- 10 from 244 +/- 11 beats/min and remained elevated for 60 min. Sensitivities of baroreflex control of heart rate and RNA were markedly impaired by PB anesthesia. In SAD rabbits, PB caused hypotension (-46 +/- 5 mm Hg), which lasted for 15 min. RNA decreased initially by 80 +/- 5%, then gradually returned toward the control level. However, at 45 min after injection of PB, RNA was still depressed significantly. Tachycardia induced by PB was abolished by SAD, i.e. heart rate actually decreased by 53 +/- 10 beats/min. These results suggest that in intact rabbits steady-state effects of PB were: no change in mean arterial pressure or RNA, and tachycardia, all due to baroreflex compensation. However, in the absence of baroreflex compensation, PB elicited hypotension, bradycardia, and a decrease in RNA.

Effects of hepatic NaCl receptor stimulation on renal nerve activity in conscious rabbits

The effects of intrahepatic NaCl or osmo-receptor stimulation on renal nerve activity were examined in chronically instrumented conscious rabbits. Combined infusions of 9% NaCl via the portal vein and distilled water via the inferior vena cava did not alter plasma osmolality or plasma Na concentration of the systemic circulation but decreased renal nerve activity. Combined infusion of 6.5% LiCl and distilled water did not have any effects on renal nerve activity. The decrease in renal nerve activity induced by portal 9% NaCl infusions was completely abolished after section of the anterior and posterior hepatic nerves. These results indicate that stimulation of the intrahepatic NaCl receptors, not of the osmoreceptors, elicits a reflex decrease in renal nerve activity, which is mainly mediated by the anterior and posterior hepatic nerves.

Suppression of renal sympathetic nerve activity during portal vein infusion of hypertonic saline

Sodium ions absorbed from the intestine are postulated to act on the liver to reflexly suppress renal sympathetic nerve activity (RSNA), resulting in inhibition of sodium reabsorption in the kidney. To test the hypothesis that the renal sympathoinhibitory response to portal venous NaCl infusion involves an action of arginine vasopressin (AVP) at the area postrema, we examined the effects of portal venous infusion of hypertonic NaCl on RSNA before and after lesioning of the area postrema (APL) or after pretreatment with an AVP V1 receptor antagonist (AVPX). Rabbits were chronically instrumented with portal and femoral venous catheters, femoral arterial catheters, and renal nerve electrodes. Portal venous infusion of 9.0% NaCl (0.02, 0.05, 0.10, and 0.15 ml.kg-1.min-1 of 9.0% NaCl for 10 min) produced a dose-dependent suppression of RSNA (-12 +/- 3, -34 +/- 3, -62 +/- 5, and 80 +/- 2%, respectively) that was greater than that produced by femoral vein infusion of 9.0% NaCl (2 +/- 3, -3 +/- 2, -12 +/- 4, and -33 +/- 3%, respectively). The suppression of RSNA produced by portal vein infusion of 9.0% NaCl was partially reversed by pretreatment with AVPX (-9 +/- 3, -20 +/- 3, -41 +/- 4, and -55 +/- 4%, respectively) and by APL (-11 +/- 2, -25 +/- 2, -49 +/- 3, and -59 +/- 6%, respectively). There were no significant differences between the effects of AVPX and APL, and the effect of APL was not augmented by AVPX. These results indicate that the suppression of RSNA due to portal venous infusion of 9.0% NaCl involves an action of AVP via the area postrema.Sodium ions absorbed from the intestine are postulated to act on the liver to reflexly suppress renal sympathetic nerve activity (RSNA), resulting in inhibition of sodium reabsorption in the kidney. To test the hypothesis that the renal sympathoinhibitory response to portal venous NaCl infusion involves an action of arginine vasopressin (AVP) at the area postrema, we examined the effects of portal venous infusion of hypertonic NaCl on RSNA before and after lesioning of the area postrema (APL) or after pretreatment with an AVP V1 receptor antagonist (AVPX). Rabbits were chronically instrumented with portal and femoral venous catheters, femoral arterial catheters, and renal nerve electrodes. Portal venous infusion of 9.0% NaCl (0.02, 0.05, 0.10, and 0.15 ml ⋅ kg-1 ⋅ min-1of 9.0% NaCl for 10 min) produced a dose-dependent suppression of RSNA (-12 ± 3, -34 ± 3, -62 ± 5, and 80 ± 2%, respectively) that was greater than that produced by femoral vein infusion of 9.0% NaCl (2 ± 3, -3 ± 2, -12 ± 4, and -33 ± 3%, respectively). The suppression of RSNA produced by portal vein infusion of 9.0% NaCl was partially reversed by pretreatment with AVPX (-9 ± 3, -20 ± 3, -41 ± 4, and -55 ± 4%, respectively) and by APL (-11 ± 2, -25 ± 2, -49 ± 3, and -59 ± 6%, respectively). There were no significant differences between the effects of AVPX and APL, and the effect of APL was not augmented by AVPX. These results indicate that the suppression of RSNA due to portal venous infusion of 9.0% NaCl involves an action of AVP via the area postrema.

Participation of baroreceptor reflexes in blood pressure and sympathetic nerve responses to a synthetic human atrial natriuretic peptide in anesthetized dogs

The effects of a synthetic alpha human atrial natriuretic polypeptide (hANP) on systemic blood pressure and renal nerve activity were studied before and after sinoaortic denervation with vagotomy in anesthetized dogs. Intravenous injection of hANP (1 microgram/kg) in animals with the neuraxis intact produced a mild decrease in systemic blood pressure and a significant increase in renal sympathetic nerve activity. However, in animals with sinoaortic denervation and vagotomy, a profound fall in blood pressure occurred after administration of hANP. Renal nerve activity in these animals was reduced significantly, in parallel with decreases in systemic blood pressure. These results indicate that activation of peripheral baroreceptors minimizes the hypotension induced by intravenous injection of hANP, and may mask at least centrally mediated cardiovascular effects of hANP.

Role of hepatic nerves in long-term control of NaCl homeostasis in Wistar-Kyoto rats.

This study was designed to investigate the effects of hepatic denervation (HD) on NaCl balance and arterial blood pressure in conscious Wistar-Kyoto rats maintained on normal or high-NaCl food. When rats were fed normal NaCl food (0.45% NaCl), HD had no significant effect on NaCl balance and arterial pressure. However, when rats were fed high-NaCl food (8% NaCl for 10 days), NaCl balance became more positive in HD rats than in sham rats. Furthermore, mean arterial pressure in HD rats (120 +/- 2 mmHg) was higher than that in sham rats (108 +/- 3 mmHg). These results indicate that the hepatic nerves play a significant role in the long-term control of NaCl balance and arterial pressure during high-NaCl food intake.

Long-term profiles of sleep-related hemodynamic changes in the postoperative chronic cat

The long-term postoperative changes in mean arterial pressure (MAP) and heart rate (HR) during sleep in cats (n = 4) were observed. In the first or second week after surgery, MAP and HR in slow wave sleep (SS) just prior to paradoxical sleep (PS) were higher than those in PS as described in previous reports. In the fourth or fifth week after surgery, the above relationships of MAP and HR between SS and PS were inverted as demonstrated in the present study. The results show that getting true physiological control data is not so simple but a complex task.

Intravenously-injected naloxone reverses the decrease in renal sympathetic nerve activity seen during hypotensive hemorrhage in conscious rabbits by acting through central mechanisms

The response of renal sympathetic nerve activity (RNA) to hemorrhage was examined in chronically-instrumented conscious rabbits. Hemorrhage was induced at a rate of 5 ml/kg per min until the mean arterial pressure fell below 40 mmHg. The mean arterial pressure then remained at around 80 mmHg until 10 ml/kg of hemorrhage (normotensive hemorrhage) before falling to below the pre-hemorrhagic control level (hypotensive hemorrhage). The RNA response showed a biphasic pattern, i.e., it increased during normotensive hemorrhage, then fell below the control level during hypotensive hemorrhage. To examine the mechanism involved in this decrease in RNA, naloxone (7.5 mumol/kg), an opioidergic receptor antagonist, was intravenously injected 1 min after the end of hemorrhage. Intravenous injection of naloxone caused an increase in mean arterial pressure and RNA to the level seen during normotensive hemorrhage. These results indicate that the decrease in RNA induced by hypotensive hemorrhage is mediated by opioidergic receptors. To determine whether the effects of naloxone are mediated via central or peripheral opioidergic receptors, naloxone was replaced by an equimolar solution of methylnaloxone, a form unable to cross the blood-brain barrier. Neither the mean arterial pressure nor RNA was significantly altered by administration of methyl naloxone. These results suggest that the effects of naloxone on both the RNA and the mean arterial pressure are mediated via central opioidergic receptors, i.e., the sympathoinhibition induced by hypotensive hemorrhage is mediated via the stimulation of central opioidergic receptors.

Chemical inactivation of the nucleus tractus solitarius abolished hepatojejunal reflex in the rat

Jejunal electrolyte absorption was measured in the jejunal loop of anesthetized rats during an infusion of 9% NaCl solution via the portal vein. Net absorption of Na and Cl, and osmolality were significantly depressed by the portal 9% NaCl infusion. The decrease in net absorption was completely abolished by hepatic denervation. In addition, bilateral chemical inactivation of the nucleus tractus solitarius (NTS) by microinjection of kainic acid abolished the depressing effect of the portal venous infusion of 9% NaCl. These findings indicate that NTS is involved in the central pathway of the hepatojejunal reflex.

Overall open-loop gain of rapidly acting arterial pressure control system in rabbits.

We estimated the overall open-loop gain of the rapidly acting arterial pressure control system without surgically or pharmacologically opening the reflex loop in rabbits. Animals anesthetized by intravenous injection of Nembutal (27.5 mg·kg−1 body weight) and heparinized were bled by 2 ml·kg−1 body weight within 1–2 s through a catheter inserted into the aortic arch. Arterial pressure change after the quick mild hemorrhage was monitored via a catheter placed in the right subclavian artery for more than 2 min. The overall open-loop gain of the lumped arterial pressure control system determined from the mean arterial pressure response to the hemorrhage was 7.3. It was almost constant over the range between 12.9 and 22.2 kPa systemic pressure.