Nobuyuki Kawazoe

Modulation of baroreflex function by angiotensin II endogenous to the caudal ventrolateral medulla

Neurons in the ventrolateral medulla (VLM) mainly determine the tonic sympathetic activity. The caudal VLM (CVLM) relays baroreflex signals to the rostral VLM. We have reported that endogenous angiotensin II (ANG II) contributes to the ongoing activity of the VLM neurons. In the present study, we examined if ANG II endogenous to the CVLM modulates the baroreflex function in anesthetized normotensive Sprague-Dawley rats. Changes in renal sympathetic nerve activity (RSNA) in response to changes in mean arterial pressure (MAP) induced by i.v. infusion of phenylephrine and nitroglycerin were recorded before and after bilateral microinjection of [Sar1, Thr8]-ANG II, an ANG II antagonist, into the CVLM. The ANG II antagonist injection into the CVLM significantly increased MAP and RSNA by 17.6 +/- 8.0 mmHg (mean +/- S.D.) and 36.3 +/- 18.1%, respectively. It also significantly increased the baroreflex sensitivity (BS) from -0.49 +/- 0.38 to -0.74 +/- 0.37%/mmHg during nitroglycerin infusion. In contrast, the BS examined by phenylephrine infusion was not altered by the pretreatment with ANG II antagonist. Injection of artificial CSF affected neither the baseline values of MAP and RSNA nor the BS. These results suggest that ANG II endogenous to the CVLM exert a modulating role in baroreflex control of RSNA.

Usefulness of Leg-Crossing for Maintaining Blood Pressure in a Sitting Position in Patients with Orthostatic Hypotension—Case Reports

The authors report a case with idiopathic orthostatic hypotension in which the patient prevents his blood pressure from fatting to a symptomatic level by leg-crossing in a sitting position. Including 4 other patients with orthostatic hypotension and 5 normal subjects, their study found that the changes in blood pressure with leg-crossing inversely correlated with those induced by assuming seated posture from a supine position. Leg-crossing may, therefore, be one of the useful nonpharmacologic measures for maintaining blood pressure in a sitting position in patients with orthostatic hypotension.

Carbamazepine-Induced Hyponatremia in a Patient with Partial Central Diabetes insipidus

A 51-year-old Japanese man was referred for the evaluation of persistent hyponatremia. The serum sodium level remained around 120 mmol/l despite mild water restriction. His past history included chronic alcoholism, myocardial infarction and lumbar disc herniation. Carbamazepine (200 mg, b.i.d.) has been used for more than 8 years for low back pain. Serum sodium returned to normal after carbamazepine was stopped, and rechallenge produced acute symptomatic hyponatremia (117 mmol/l) on day 2 after a total dose of 600 mg. Hepatic, renal and endocrine function were within normal limits, and the response to a water load (20 ml/kg) was also normal. Partial central diabetes insipidus was diagnosed by his response to water restriction and nasal desmopressin administration. Polyuria and hypernatremia were not evident in this case, probably due to a combination of low solute intake and low, but not deficient, levels of plasma ADH. This case demonstrates that carbamazepine may cause acute hyponatremia even in central diabetes insipidus, probably by sensitizing the distal renal tubules.

Chronic Hypovolemia Associated with Accelerated Hypertension and Orthostatic Hypotension in a Patient on Continuous Ambulatory Peritoneal Dialysis

We report a patient with nondiabetic end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD) associated with chronic hypovolemia. Despite the administration of nilvadipine, the patient showed accelerated hypertension and concomitantly orthostatic hypotension. Plasma renin activity was markedly high, and blockade of angiotensin II action by captopril or an angiotension II antagonist decreased the supine blood pressure. This indicated that the enhanced activity of the renin-angiotensin system was the principal cause of the supine hypertension. The plasma concentration of norepinephrine was also very high. After correction of hypovolemia by blood transfusion, the enhancement of the renin-angiotensin system and high plasma norepinephrine level were reduced, and symptomatic orthostatic hypotension disappeared. The accelerated hypertension was easily controlled by the administration of low-dose captopril and nilvadipine. These findings suggest that chronic hypovolemia related to the intractable supine hypertension as well as orthostatic hypotension. Hypovolemia-induced enhancement of the renin-angiotensin system and sympathetic nerve activity may cause vasoconstrictive hypertension in patients on CAPD.

Alpha2-Adrenoceptors in Brain and Kidney during Development of Hypertension in Dahl-Iwai Salt-Sensitive Rats

Background: Both renal and extrarenal factors have been considered to contribute to the development of hypertension in Dahl salt-sensitive rats, but contents of both factors have not been established precisely.Aim: To clarify the role of those factors in the sympathetic nervous system, we examined the regulation of alpha2-adrenoceptors in the lower brainstem and the renal tubular basolateral membranes simultaneously during the development of salt-induced hypertension in Dahl-lwai salt-sensitive rats.Methods: Dahl-lwai salt-sensitive or resistant rats were fed a high (8.0 % NaCI)- or low (0.3 %)- salt diet from 4 to 6 or 10 weeks of age. At 4, 6 and 10 weeks of age, the plasma membranes of the lower brainstem and the renal tubular basolateral membranes were obtained simultaneously and alpha2-adrenoceptors were quantified by a radioligand binding assay using 3H-rauwolscine.Results: In the salt-sensitive rats, systolic blood pressure was significantly higher in those fed a high-salt diet than in those fed a ...

Renin responses in patients with orthostatic hypotension: case reports.

In orthostatic hypotensive patients renin is reported to increase in response to head-up tilt unless the lesion involves postganglionic sympathetic efferent nerves. The authors examined responses of plasma renin activity (PRA) to acute blood pressure reduction in 4 patients with orthostatic hypotension. When the coexistence of normal plasma norepinephrine (PNE) and normal or high-nor mal pressor response to alpha stimulant is considered to be a sign of preserved function of postganglionic fibers, 2 of the patients had sympathetic lesions mainly confined to central and/or preganglionic fibers. They were diagnosed as having multiple system atrophy (MSA). The other 2 were diagnosed as having idiopathic orthostatic hypotension with possible postganglionic lesions. Al though 1 MSA patient showed an increase in PRA from 2.0 to 4.7 ng/mL/hr in response to the tilt, the other MSA patient showed no PRA response to the tilt. The head-up tilt did not provoke an apparent PRA response in patients with idiopathic orthostatic hypotension. The authors infused sodium nitroprusside (SNP) in the 3 patients whose PRA did not respond to the head-up tilt. The infusion decreased blood pressure by 40 mmHg or more, but PRA responses were inappropriately small or suppressed. In all cases, PNE did not respond at all to the head-up tilt and to the infusion of SNP. These findings suggest that possible preservation of postganglionic fibers does not necessarily indicate an intact responsiveness of PRA. The PRA profiling may not be an accurate pre dictor for the site of the fiber degeneration in orthostatic hypotension.

LACK OF SYMPATHETIC AUGMENTATION IN RESPONSE TO INTRAVENOUS LOAD OF GLUCOSE IN RABBITS

1. We investigated a link between sympathetic nervous function and carbohydrate metabolism by measuring renal sympathetic nerve activity in response to intravenous load of glucose in α‐chloralose‐urethane anaesthetized rabbits.