Jae-Sik Park

Gene expression of central and peripheral renin-angiotensin system components upon dietary sodium intake in rats.

The effects of dietary sodium intake on the gene expression of the renin-angiotensin system (RAS) were investigated in rat central and peripheral tissues in a single set of experiment. Northern and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques were used to detect mRNA expression in rats fed a low- or a high-sodium diet (5 or 500 mmol Na+/kg diet) for 20 days. Plasma and renal renin levels were elevated in rats maintained on the low-sodium diet. Sodium deprivation enhanced the expression of angiotensinogen, renin, AT1A and AT1B receptor subtypes in the hypothalamus, but suppressed them in the brainstem. Kidney and adrenal levels of those mRNAs were also enhanced in the sodium-restricted rats. Both AT1A and AT1B mRNAs changed in a similar magnitude in each tissue examined upon dietary sodium intake. AT1A was the predominant receptor subtype of AT1 in all the tissues examined in the present study except the adrenal gland. The present study demonstrated that dietary sodium modulated the gene expression of the RAS components in the central and peripheral tissues. It also showed that the RAS components in the brainstem and hypothalamus were differentially expressed upon sodium deprivation. This suggests different roles of the RAS in these tissues in maintaining body fluid homeostasis in response to different sodium intakes.

Effects of intracisternal injection of interleukin-6 on nociceptive jaw opening reflex and orofacial formalin test in freely moving rats

The present study was performed to investigate the effects of central cytokines on the modulation of nociception in the orofacial area. To achieve this purpose, a nociceptive jaw opening reflex and an orofacial formalin test were monitored before and after intracisternal administration of interleukin-6 (IL-6) in freely moving rats. In the nociceptive jaw opening reflex, the digastric electromyogram (dEMG) was not significantly changed after intracisternal injection of 200 pg and 2 ng IL-6. However, 20 ng IL-6 suppressed dEMG to 74+/-7% of the control values. In the inflammatory orofacial formalin test, intracisternal injection of 200 pg and 2 ng IL-6 did not change the number of noxious behavioral responses produced by formalin injection. However, 20 ng IL-6 injected intracisternally significantly increased the number of noxious behavioral responses produced by formalin. The hyperalgesic action of intracisternal IL-6 in the orofacial formalin test was blocked by pretreatment with interleukin-1 (IL-1) receptor antagonist. These results suggest that IL-6 injected intracisternally modulates the transmission of nociceptive information in the orofacial area. However, the hypo/hyper-algesic response of central cytokines seems to depend on the orofacial pain model. The hyperalgesic response of central IL-6 seems to be mediated by the IL-1 receptor.

Effect of brain angiotensin II AT1, AT2, and cholinergic receptor antagonism on drinking in water-deprived rats

The physiological role of brain Ang II and acetylcholine in mediating water deprivation-induced drinking was assessed in male Sprague-Dawley rats. Specific receptor antagonists were intracerebroventricularly (i.c.v.) administered in 48-h water-deprived rats. When water was given 20 min after i.c.v. injection, PD 123319 almost totally blocked the drinking response. However, losartan and CGP 42112A produced an approx. 20% inhibition of water intake. Central blockade of AT1 receptor with KR 31080 and cholinergic receptor with atropine attenuated water intake more than 50% which was significantly greater than inhibition produced by losartan and CGP 42112A. Atropine given alone or mixed with losartan and CGP-42112A produced a similar magnitude of inhibition of water intake. When water was given 90 min after i.c.v. injection, losartan or CGP-42112A produced a significantly greater inhibition of water intake than when water was given 20 min after injection. The present results suggest that both the central angiotensinergic and cholinergic system play an important role in the physiological drinking response after water deprivation. Both brain AT1 and AT2 receptors are involved in dehydration-induced drinking, but relative contribution of the receptors remains to be clarified.

Effects of chronic central administration of losartan on the cardiovascular and hormonal responses to hemorrhage in conscious rats

Our objective was to assess the effects of chronic central angiotensin II (Ang II) blockade on the basal regulation of blood pressure, heart rate (HR), arginine vasopressin (AVP), renin, epinephrine (EPI), norepinephrine (NE) and on cardiovascular and hormonal responses to hemorrhage in conscious rats. Losartan (4 micrograms/h), or artificial cerebrospinal fluid (aCSF), was chronically infused into a lateral ventricle by using an osmotic minipump for 6 days at a rate of 1 microliter/h. Compared with aCSF controls, chronic losartan treatment significantly decreased the basal level of blood pressure (from 117 +/- 2.3 to 106 +/- 2.2 mmHg, P < 0.01) and increased the HR (from 357 +/- 3.7 to 410 +/- 6.6 beats/min, P < 0.01). Plasma renin concentration increased 3-fold (from 6.1 +/- 0.6 to 19.2 +/- 1.6 ng.ml(-1).h(-1), P < 0.01). Basal levels of AVP, EPI and NE were not different between two groups. Blood pressure immediately after hemorrhage and its compensatory recovery following hemorrhage was not different in both groups. Immediately after hemorrhage, however, in the losartan-treated rats, the HR was distinctly lower than that of aCSF controls, even at 10 min after hemorrhage. Hemorrhage produced a significant increase in the plasma concentrations of AVP, renin, EPI and NE. Chronic losartan treatment markedly augmented the AVP, renin and EPI responses to hemorrhage. These results strongly suggest that Ang II acting through AT1 receptors in the brain plays a significant physiological role in the regulation of basal blood pressure, HR and renin release. In addition, centrally acting Ang II may be one of the important mediators for cardiovascular regulations and hormone releases in response to hemorrhage.