수입소동맥 저항과 수출소동맥 저항의 상호 작용에 대한 연구

양훈모,민영기,이정범 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

It has generally been accepted that efferent arteriolar constriction increase GFR. However, it has also been shown in mathematical studies that increases in efferent arteriolar resistance beyond some extent causes GFR to decrease. The aim of the present study is to investigate the occurrence of physiological and/or pathophysiological conditions in which GFR is decreased by efferent constriction. The renal hemodynamic data obtained by several investigators were analyzed with a mathematical model of single nephron GFR (SNGFR). The glomerular model is based on a simulation of flow along a glomerular capillary with negligible resistance and uniform ultrafiltration coefficient (K_(f), 0.09 nl · sec^(-1) · mmHg^(-1)). The data analyzed are from rats which have been shown to achieve filtration pressure equilibrium(FPE) during filtration along the glomerular capillary. The hemodynamic states of rat kidney is characterized by a high K_(f), low RBF, and high vascular resistance. In these animals, inhibition of the renin-angiotensin system was associated with increases in GFR. This was mainly contributed to the increase in K_(f). Analysis with the present model has shown that lowered efferent arteriolar resistance during angiotensin inhibition augmented GFR response to K_(f). The analysis of the data obtained by manipulating efferent resistance during aortic constriction demonstrated the importance of pregiomerular resistance(R_(PRE)) related to efferent resistance (R_(E)). in this hemodynamic condition. The FPE which determines the sensitivity of SNGFR to SNBF and K_(f) is attained nearer the afferent end as R_(PRE) increases further: On the other hand, R_(PRE) had no effect on FPE. In conclusion, certain physiological manipulation affects R_(PRE) and K_(f) in such fashion that a decrease in R_(E) may have a beneficial effect on GFR and vice versa. This analysis indicates that it is not limited to theoretical importance; it demonstrated that in rat kidneys which have low flow and high afferent resistance the efferent arteriolar dilation can be associated with the promotion of GFR.

근육세뇨관 수분 및 이온 이동에 대한 모델

양훈모,송혜섭,민영기 순천향의학연구소 1999 Journal of Soonchunhyang Medical Science Vol.5 No.2

본 연구는 세뇨관 벽을 통하여 물과 이온이 이동하는 현상을 수학적 모델에 근거하여 수행하였다. 세포측막, tight junction, 기저막으로 구성된 측간질 공간으로의 염분이동은 삼투현상에의해 동시에 수분이동을 유발한다. 이로인한 수분에 공간내 증가는 정수합을 증가시켜 Na, Cl, HCO3 에 대한 반사계수가 0 이고 투과성이 매우 높은 기저막을 통해 용액이 유출된다. 동반이동 가능성과 비평형 열역학 이론을 포함한 본 모델을 이용하여 tight junction의 이온투과성과 반사계수가 물과 이온 이동에 미치는 영향을 조사해 본 결과는 다음과 같다. 1. 수분의 전도성(Lp)은 100배 이상하여야 삼투압에 의한 수분이동이 전체 수분이동에 영향을 미칠 수 있다. 2. 관강 측과 기저측 세포막은 반사계수가 1이기 때문에 세포를 관통하는 convective ion flux에는 영향이 없었다. 3. 관강내 액과 측공간 액사이에는 높은 HCO3 농도 경사가 유지되고 있기 때문에 HCO3에 대한 높은 반사계수는 삼투적 수분 흡수에 필수적이다. 4. Cl의 반사계수의 감소는 수분흡수를 증가시켜 Cl 재흡수도 증가시켰다. 동시에 전기적 확산에 의해 Na 재흡수도 증가하였다. 5. 전반적인 반사계수의 감소는 수분 재흡수는 감소 시켰으나 용질 재흡수는 증가시켰다.

개에서 17-ODYA가 신혈류량 자동 조절에 미치는 영향

양훈모,민영기,박중섭 순천향의학연구소 1999 Journal of Soonchunhyang Medical Science Vol.5 No.1

17-ODYA is a potent inhibitor of the formation of 20-hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acids and dihydroeicosatetraenoic acids by renal cortical microsomes. This study characterized the effects of intrarenal infusion of 17-ODYA on renal blood flow (RBF) and autoregulation of RBF. Seven dogs were prepared for the measurements of RBF, mean systemic and renal perfusion pressure. The renal perfusion pressure was able to be adjusted to desired levels by an inflatable supra-aortic occluder. Intrarenal infusion of 17-ODYA produced a diuresis and a natriuresis but no change in RBF. 17-ODYA had no effect on autoregulation of RBF: Both the plateau and steep portrions. of the autoregulatory curves were identical to control. Thesholds for lower limit of autoregulation were 72±4 and 72±5 mmHg during control and 17-ODYA and not significantly different from each other. These results suggest that endogenous cytochrome P-450 metabolites of AA do not influence RBF autoregulatory capacity in dogs.

뇌 해마의 복측 또는 배측 부분이 제거된 흰쥐 중격핵의 신경전달물질

양훈모,김종규,한영길,민영기 순천향의학연구소 1999 Journal of Soonchunhyang Medical Science Vol.5 No.1

This study was planned to analyze amino acids in the septal nucleus of dorsal and ventral hippocampectomized rats by high performance liquid chromatography (HPLC). Male albino rats were used. Under chloral hydrate anesthesia (20%, 2 ml/kg body weight), a hole was made in each parietal bone about 4 mm lateral to the sagittal suture, and 4 mm rostral to the lambda suture. The cortical tissue on each side was removed and, through this opening, the hippocampal tissue anterodorsal and posteroventral to the hippocampal flexures on both sides was removed by aspiration. This preparation served as the dorsal and the ventral hippocampal animals, respectively. The cortical control animal received the same surgery short of hippocampectomy. The normal rats served as normal control animal. One day later, the animals were sacrificed by decapitation in the cold room. Two to three milligrams of tissue was obtained form the septal nucleus in one side of the brain. The tissue samples were homogenized and centrifuged. Then content of each amino acid was measured by HPLC form the brain tissue. The contents of aspartate and glutamate were decreased significantly more in the dorsal and ventral hippocampal groups than in the normal and the cortical control groups. The contents of glutamate were decreased significantly more in the ventral hippocampal group than in the dorsal hippocampal, while there were no significant differences between the two control groups. It is inferred form the above mentioned results that glutamate and aspartate may be used as excitatory transmitters in septal nucleus, and that the dorsal hippocampus may be facilitatory to the septal nucleus, but the ventral hippocampus would be inhibitory/facilitatory to the cortex.

신장내 국소혈류량 조절에 대한 신교감신경의 영향

양훈모,민영기,김동진,송호연,송윤섭 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.2

Control of blood pressure is affected by regulation of intrarenal blood flow. Renal sympathetic nerve simulation inhibits pressure-depressor mechanism of kidney. This antidepressor mechanism was known as happening to due to a decrease the blood supply of renal medulla. It is not known whether renal sympathetic nerve innervation of renal medulla is and it affects regulation of medullary blood flow. We tried to measure total renal blood flow(TRBF), cortical blood flow(CBF), papillary blood flow(PBF) by ultrasonic and laser Doppler techniques in Wistar rats during 3 kinds of renal sympathetic nerves stimulation. The simulation orders are tried randomly and each stimulation period is 15 minute. TRBF and CBF decreased at 1 Hz by 2 and 2%, 3Hz by 18 and 15%, 5Hz by 49 and 44%, respectively as similar to each other. But PBF increased by 1% at 1 Hz and 4% at 3 Hz, while it decreased by 4% at 5 Hz. Therefore, it seems superficial renocortical and total renal blood flows are closely regulated by renal sympathetic nerves with increasing vasoconstriction at 5 Hz, onthe other hand while medullary blood flow seems to be under strong local control, tending to offset neurogenic flows restrictions.

고 사구체전 저항의 신장에서 수출소동맥 이완에 대한 신혈역학적 반응 : 수학적 접근

양훈모,주명찬 순천향의학연구소 1998 Journal of Soonchunhyang Medical Science Vol.4 No.1

To progressive increases in efferent arteriolar resistance (RE), GFR responds with an initial increase followed by a decrease. The biphasic response implies that the response of GFR to RE varies depending on the renal hemodynamic conditions. We studied, with a glomerular model, the mechanism of deterioration of renal function during angiotensin I converting enzyme inhibitor (ACEI) in the kidney with renal artery stenosis. The glomerular model was based on a simulation of flow along a glomerular capillary with negligible resistance and uniform ultrafiltration coefficient (kf, 0.09 nl·sec-1·mmHg-1). The control preglomerular resistance (RPRE) and RE were 0.071 and 0.081 mmHg·min·ml-1, respectively. The effect of renal artery stenosis is to increase RPRE by inserting a fixed stenotic resistance in series with the afferent arteriolar resistance, and RPRE which is the sum of the resistances of stenosed renal artery and afferent arteriole is increased in the kidney with stenosed renal artery. Since the higher RPRE is associated with greater reduction in GFR in response to reduction in RE, the kidney with stenosed renal artery will respond with severer decrease in GFR to postglomerular vasodilation. In addition, the preglomerular vasodilation which accounts for the major compensatory response to renal hypotension in the normal kidney becomes less and less effective in recovering PG and GFR during a decrease in renal artery pressure as the resistance caused by the stenosis becomes greater. The model has shown that these two factors contributed to the greater reduction in GFR (34ml·min-1 during renal artery stenosis vs. 46.5ml·min-1 during control) despite an increase in kf (40%) during ACEI in the kidney with renal artery stenosis (resistance; 0.082 mmHg·min·ml-1). In conclusion, severer deterioration of renal function in response to ACEI administration in the kidney with renal artery stenosis results from the reduced ability of RPRE to decrease in response to hypotension and the increased sensitivity of GFR to a decrease in RE when RPRE is increased.

요관압 상승시 신혈류량 조절에 prostaglandin이 미치는 효과

민영기,양훈모,김종규,이석호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Higher ureteral pressure than in normal condition causes increase in renal blood flow (RBF) and partial impairment of the autoregulation of RBF. Higher ureteral pressure increased renal prostaglandin production, it is not clear whether or not it is also responsible for partial impairment of the autoregulation of RBF. Therefore, we investigated the role which prostaglandin play in the autoregulation of RBF, studying the interaction between ureteral pressure and RBF autoregulation may reveal the role of prostaglandin in tubuloglomerular feedback. For the purpose of this experiment, six anesthetized mongrel dogs were prepared for the measurements of RBF, mean systemic and renal arterial pressure (RAP) and the manipulation of ureteral pressure to 0 cmH20, 20 cmH20 and 40 cmH20. The autoregulation curves were determined during both control and elevation of the ureteral pressure, before and after the pretreatment with indomethacin, a cyclooxygenase inhibitor. The desired ureteral pressure was achieved by vertically elevating the water-filled reservoir connected to the ureteral catheter to 20 cm and 40 cm above the kidney level. In response to the elevation of the ureteral pressure, RBF increased from 167±11 ml/min to 185±8 ml/min, 204±11 ml/min respectively and the renal arterial pressure and the systemic arterial pressure didn't change significantly. During 0 mmHg of ureteral presure threshold pressure of RBF autoregulation was 59±3 mmHg. On the other hand, during 20 cmH20, 40 cmH20 of ureteral pressure, the autoregulation curves shifted upward and rightward from control, threshold pressure is elevated by 74±3 mmHg. The pretreatment of the dogs with indomethacin failed to affect the lower limit of RBF autoregulation during both control (63±5 mmHg) and the elevated ureteral pressure (77±5 mmHg). Since RBF failed to increase in response to the elevated ureteral pressure, RBF autoregulation curves obtained during the elevated ureteral pressure shifted only rightward from indomethacin control. The results indicate that the increased intrarenal level of prostaglandin by increased ureteral pressure or prostaglandin-induced vasodilation does not appear to bear any relation to the reduction in the autoregulatore capacity during elevated ureteral pressure. It seems that the partial impairment of the autoregulation during acute ureteral obstruction is due to the consumption of tubuloglomerular feedback mechanism at 0 mmHg of ureteral pressure and that prostaglandin is neither mediator nor effector of tubuloglomerular feedback mechanism.

Tight Junction의 투과성 변화가 근위세뇨관 재흡수에 미치는 영향

김종규,양훈모,심상용,민영기 순천향의학연구소 1999 Journal of Soonchunhyang Medical Science Vol.5 No.1

The proximal tubular model is based on a simulation of fluid and ion transport across the tubular wall. This model includes a space between the basolateral cell membrane, tight junction and the basement membrane as lateral interstitial space. Salt transport into the interspace would induce an osmotic water flow across this membrane. The accumulation of salt and water solute within the interspace would create a sufficient hydrostatic pressure to drive this solution out across the permeable basement membrane ( σ, reflection coefficient = 0). We tested with this model the influence of σ and permeability characteristics (Pi) of the proximal tubular epithelium on transmembrane volume(Jv) and ion(Ji) fluxes and potential difference. Epithelial transport mechanism specifically included the possibility of coupled transport processes and the linear theory of nonequilibrium thermodynamics. The model predicted the following results. An increase in PNa decreased the reabsorption of all the major ions and water due to diffusion of Na into the lumen. An increase in Pa had an opposite effect: The electrochemical gradient favoring chloride reabsorption was established shortly after the initial segment. PHCO3 was ineffective in affecting proximal tubular transport of water and ions. While σNa, and σcl had very little effect on the proximal tubular transport, σHCO3 had a significant effect on JNa, Ja but not on JHCO3. It was due to an increase in convective flow of sodium and chloride secondary to an increase in Jv. It is concluded that the changes in σi or Pi for specific ions can have a differential effect on tubular transport since ion fluxes are the sum of both diffusive and convective components; the electrochemical gradient affects the former, and water flux and σi between which there is a kind of reciprocal relation affect the latter.

enalapril의 혈압하강효과에 대한 renomedullary depressor system의 역할

민영기,양훈모,김종규,이석호 순천향의학연구소;Soonchunhyang Medical Research Institute 2000 Journal of Soonchunhyang Medical Science Vol.6 No.1

It has long been recognised that renin-angiotensin system(RAS) takes part in blood pressure control. It was previously known that the physiological effects of the renomedullary depressor mechanism are in virtually all aspects the very opposite of those of RAS. Muirhead proposed that there was a negative-feedback interaction between two systems, RAS and renomedullary antihypertensive depressor system, and they balance each other. If true, as the suppression of angiotensin Ⅱ(ANG Ⅱ)by angiotensin converting enzyme(ACE) inhibitor activates the renomedullary antihypertensive function, we can assume the blood pressure lowering effects of ACE inhibitor due to an increased secretion of medullary depressor substance. After rats with intact and chemically destroyed renal medulla received either saline or the ACE inhibitor, mean arterial pressure(MAP) was clearly decreased after ACE inhibitor administration in controls with intact medulla, but MAP in rats with chemically destroyed renal medullar was not changed. According to these results, we can come to a conclusion that renomedullary depressor substance plays an important role to normal blood pressure control.

L - NAME 주입시 신 교감신경이 신혈류량 변화에 미치는 영향

민영기,양훈모,이석호,김종규 순천향의학연구소 2000 Journal of Soonchunhyang Medical Science Vol.6 No.2

Recently it is known renal medullar will be play a important role of blood pressure control and pressure natriuresis. Renomedullary antihypertensive mechanism is activated by increasing perfusion pressure of kidney and can be inhibited by sympathetic nerve stimulation or blockade of nitric oxide(NO) formation. It is important to know what is affect on renal regional blood flow, especially renal medullary blood flow(MBF). For the purpose of investigating the effect of the renal sympathetic nerve on regional blood flow during infusion of blocking NO synthesis(by N^(ω)-nitro-L-arginine methylester:L-NAME) in spontaneous hypertensive rat(SHR) and Wistar rats normal control, Mean arterial pressure(MAP), total renal blood flow(TRBF), midcortical blood flow(CBF), inner medullary blood flow were measured in innervated or denervated renal sympathetic nerve group of SHR and Wister rats. All group that received the L-NAME were seen increasing MAP while TRBF, CBF and MBF decreased and the decrease of TRBF in SHR is more marked than in Wistar rat. In spite of increasing the MAP, MBF in all four group decreased, respectively C: 220 ± 3 U, 205 ± 2 U Wi : 215 ± 4 U, 165 ± 12 U Wd :218 ± 3 U, 170 ± 10 U Si :195 ± 4 U, 98 ± 15 U Sd : 200 ± 3 U, 120 ± 14 U, especially the most remarkable decrease about 50 % in SHR innervated group. Thus, according to these result, NO seems to maintain the MBF and the partial interaction between renal sympathetic nerve and NO in medullary blood flow can be suggested in innervated SHR.