|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1996 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1995 : ¥1,500,000 (Direct Cost : ¥1,500,000)
The mechanisms underlying salt-dependent hypertension are not entirely known. Renal sympathetic nerve activity (RSNA) has a direct effect on the control of renal blood flow, renin release and urinary sodium excretion.
1.We have recorded RSNA in free-moving Dahl salt sensitive (DS) and salt-resistant (DR)-rats on a low NaCl diet.
(1) Under resting conditions, two types of discharge patterns were seen, a grouped cardiac-related discharge (GD) and a non-grouped irregular discharge (NGD). The GD was inhibited by i.v.administration of phenylephrine chloride, while the NGD was not. Both GD and NGD were seen in DS and DR rats and both were completely abolished by i.v.administration of the ganglionic blocker, hexamethonium chloride.
(2) l.c.v.infusion of hypertonic NaCl solution significantly increased arterial blood pressure and decreased RSNA compared with the resting levels in both Dahl-R and Dahl-S rats. However, the responsiveness of RSNA to NaCl did not differ in either group. Heart rate did not significantly change.
(3) During 0.3 M NaCl infusion, water intake in Dahl-S rats was diminished compared with that in Dahl-R-rats.
2.Next, using conscious Sprague-Dawley rats, we have examined responsiveness of RSNA in response to central salt loading. The inhibitory response of RSNA following i.c.v.administration of hypertonic NaCl solution were,
(1) greatly attenuated under pentobarbital anesthesia.
(2) enhanced in conscious rats not access to water.
(3) observed in sinoaortic denervated (SAD) conscious rats.
(4) significantly attenuated by pretreatment with vasopressin V_1 antagonist (OPC-21268, i.v.) but not V_2 antagonist (OCP-31260).