Studies on the Mechanism of Renal Action of Centrally-administered TFMPP in Rabbits / 대한신장학회잡지

It has been known that central tryptaminergic system is closely related with the regulation of renal function, and that central 5-HT1 receptors mediate diuresis and natriuresis, whereas central 5-HT2 and 5-HT3 receptors mediate antidiuresis and antinatriuresis. Among many subtypes of 5-HT1 receptors, central 5-HT1A subtype has been suggested to exert diuretic and natriuretic effets. Further, it was recently observed that TFMPP, 5-HT1B agonist, elicited profound diuresis and natriuresis when administered intracerebroventricularly(icv). Present study is therefore undertaken to delineate the mechanism involved in the natriuresis and diuresis induced by icv TFMPP, employing the denervated and vagotomized rabbits. The influence of icv TFMPP on the plasma level of ANP was also observed. TFMPP 250 microgram/kg icv produced marked diuresis and natriuresis. Renal hemodynamics showed significant increase only in the first 10-min period after administration and thereafter tended to recover. However, natriuretic action lasted even after the increased renal hemodynamics returned to the control level, suggesting the decreased Na reabsorption in the tubules by humoral natriuretic factors. Systemic blood pressure transiently increased. In rabbits in which one kidney is denervated, with the contralateral intact as the control kidney, the denervated kidney also responded with natriuresis and diuresis like that of the normal rabbit. The contralateral kidney responded with typical diuretic and natriuretic effects, along with the marked increased of renal hemodynamics. The plasma ANP, one of humoral natriuretic factors, increased after administration of icv TFMPP, peaking at about 15min. In bilaterally vagotomized rabbits, the natriuretic and diuretic effects produced by icv TFMPP were greater than that of the normal rabbits. These observations suggest that the natriuresis and diuresis elicited by icv TFMPP result from the inhibition of tubular Na reabsorption mainly through mediation of ANP. It has been also suggested that vagus nerve might exert inhibitory influence on the diuretic action of icv TFMPP, because the renal effects was augmented in the vagotomized rabbits.

Influence of Intracerebroventricular Kallikrein and Lys-bradykinin on the Rabbit Renal Function / 대한신장학회잡지

The renal function is under regulatory influence of central nervous system, in which various neurotransmitter and neuromodulator systems take part, and it has been known that kallikrein-kininogen- kinin system exists also in the brain, but its physiological role remains to be explored. This study was, therefore, undertaken to delineate the possible role of central kinin system in the regulation of renal function. Kallikrein given into a lateral ventricle(icv) of rabbit brain in doses ranging from 3 to 30 microgram/kg icv elicited increases in Na excretion and the fraction of filtered sodium excreted(FENa), as well as in urine flow rate. K excretion, however, did not parallel the Na excretion, but tended to decrease when the natriuresis reached its peak. Renal blood flow and glomerular filtration did not significantly change. Neither did free water reabsorption significantly change, but tended to decrease. The systemic blood pressure slightly increased. When 30 microgram/kg kallikrein was given intravenously, all the parameters of renal function and systemic blood pressure did not show any increase but decrease, primarily by decreased renal hemodynamics, resulting from transient hypotension. In experiments in which the plasma ANP was measured, the ANP level markedly increased, reaching more than 5 times the control value 25min after 30 microgram/kg icv, and lasting until the end of the experiment at 80min. The renal nerve activity increased with kallikrein, 30 microgram/kg icv, peaking at 1 min but it remained slightly increased until about 40 min, and then slightly declined. This indicates that the increased renal nerve activity may have antagonized or ameliorated the natriuretic effect of icv kallikrein. Lys-bradykinin(kallidin), a cleavage product from kallidinogen by kallikrein, when given icv in doses of 0.3 to 30 microgram/kg also produced increased Na excretion and diuresis. When CHA, a kallikrein inhibitor, was given icv in doses of 3-30 microgram/kg, elicited antidiuresis and antinatriuresis. However, pretreatment with CHA tended slightly to suppress the kallikrein effect. These results indicate that the central kallikrein- kinin system is involved in the central regulation of renal function, the activation of the system in the CNS resulting in increased natriuresis and diuresis, which are related to increased plasma ANP level, with the possible antagonistic effects of increased renal nerve activity.

Contractile effects of hemoglobin-free human cerebrospinal fluid on isolated porcine cerebral arteries

To elucidate the mechanism involved in the cerebral vascular spasm following subarachnoid hemorrhage (SAH), the effects of the cerebrospinal fluid (CSF) obtained from the SAH patients on the resting tension and its influence on the contractile responses to various vasoactive agents and to hypoxia were investigated in isolated porcine cerebral arteries. All the CSFs containing hemoglobin (Hb) produced contraction and some Hb-free CSFs also elicited contraction. When the Hb-free CSF was separated by microfilter, the filtrate of < 30,000 MW did not produce contraction, while the fraction above 30,000 MW elicited more marked contractile responses than the unfractionated CSF. The CSF contraction was significantly attenuated in the presence of indomethacin or nimodipine, whereas the contractions induced by KCl, prostaglandin F2alpha (PGF2alpha), or endothelin-1 (ET-1) were not affected by the CSF pretreatment. However, the contractile responses induced by 5-hydroxytryptamine (5-HT) and phenylephrine (PE) were markedly potentiated by the pretreatment. Hypoxia-induced vasoconstriction was significantly potentiated by the pretreatment with either unfractionated CSF or the CSF fraction of above 30,000 MW. These results suggest that unknown vasocontractile substance(s) exists in the Hb-free CSF and that the substance, with its MW above 30,000, is activated by hypoxia and acts synergistically with 5-HT and PE, and that extracellular calcium influx and cyclooxygenase are also involved in the cerebral vasoconstrictory effect of Hb-free CSF.

Natriuresis induced by intracerebroventricular diazepam in rabbits

The renal function is under regulatory influence of central nervous system (CNS), in which various neurotransmitter and neuromodulator systems take part. However, a possible role of central GABA-benzodiazepine system on the central regulation of renal function has not been explored. This study was undertaken to delineate the renal effects of diazepam. Diazepam, a benzodiazepine agonist, administered into a lateral ventricle (icv) of the rabbit brain in doses ranging from 10 to 100 microgram/kg, elicited dose-related diuresis and natriuresis along with improved renal hemodynamics. However, when given intravenously, 100 mug/kg diazepam did not produce any significant changes in all parameters of renal function and systemic blood pressure. Diazepam, 100 mug/kg icv, transiently decreased the renal nerve activity (RNA), which recovered after 3 min. The plasma level of atrial natriuretic peptide (ANP) increased 7-fold, the peak coinciding with the natriuresis and diuresis. Muscimol, a GABAergic agonist, 1.0 mug/kg given icv, elicited marked antidiuresis and antinatriuresis, accompanied by decreases in systemic blood pressure and renal hemodynamics. When icv 0.3 microgram/kg muscimol was given 3 min prior to 30 mug/kg of diazepam icv, urinary flow and Na excretion rates did not change significantly, while systemic hypotension was produced. These results indicate that icv diazepam may bring about natriuresis and diuresis by influencing the central regulation of renal function, and that the renal effects are related to the increased plasma ANP levels, not to the decreased renal nerve activity, and suggest that the effects may not be mediated by the activation of central GABAergic system.

Renal functional responses to a centrally-administered 5-HT-1A agonist in the anesthetized rabbits

Central tryptaminergic system has been shown to play an important role in the regulation of renal function: 5-HT-1 (5-hydroxytryptamine-1) receptors might seem to mediate the diuresis and natriuresis, whereas the 5-HT-2 and 5-HT-3 receptors mediate the antidiuretic and antinatriuretic effects. This study attempted to delineate the role of central 5-HT-1A subtype in the regulation of rabbit renal function by observing the renal effects of intracerebroventricularly(icv)-administered PAPP (p-aminophenylethyl-m-trifluoromethylphenyl piperazine, LY165163), a selective agonist of 5-HT-1A receptors. PAPP in doses ranging from 40 to 350 microgram/kg icv induced significantly diuresis, natriuresis, and kaliuresis, along with increased renal perfusion and glomerular filtration. Systemic blood pressure was also increased. Free water reabsorption (T-cH-2O), a measure of ADH (antidiuretic hormone) secretion, was increased also. Intravenous 350 microgram/kg of PAPP elicited antidiuresis and antinatriuresis together with decreased blood pressure, thus indicating that the effects of icv PAPP were brought about through the central mechanisms, not by direct peripheral effects of the drug on kidney. Ketanserin, a selective 5-HT-2 antagonist, 40 microgram/kg icv, did not affect the renal effects of the icv PAPP. Methysergide, a non-selective 5-HT-1 antagonist, also did not block the renal functional responses by the icv PAPP. NAN-190, a 5-HT-1A antagonist, also did not antagonized the renal action of the icv PAPP. However the increased free water reabsorption was abolished by both methysergide or ketanserin pretreatment. The increments of blood pressure by icv PAPP was blocked only by NAN-190 pretreatment. These observations suggest that the central 5-HT-1A receptor might be involved in the central regulation of rabbit renal function by exerting the diuretic and natriuretic influences.

The Last Fifty Years of Western Medicine in Korea: Korean Society of Pharmacology

No abstract available.

Amiloride Action on Oxamide Treated Kidneys and lnfluence of Oxamide on the Distribution of lntrarenal Blood Flow / 대한비뇨기과학회지

In an attempt to obtain evidence in the mechanism of stone formation, the effectiveness of Amiloride. a K-sparing diuretic known to act on the distal nephron. on the kidney with oxamide-induced urolithiasis was investigated. Futhermore. the influence of stone formation on the distribution of intrarenal blood flow and the effect of Amiloride on them were also studied. Most prominent derangements of renal function observed during stone formation were decreases of both C(PAH) and C(cr) indicating the curtailment in renal hemodynamics. The oxamide-treated kidney also responded to Amiloride with typical natriuresis and antikaluresis. in the same fashion with normal kidneys. The experiments in which the intrarenal blood flow distribution was measured by PAH-extraction technique raveled that mainly the cortical blood flow was curtailed, whereas non-cortical blood flow (medullary flow) did not change during oxamide-stone formation. Amiloride did not influence the intrarenal b100d flow distribution both in normal and oxamide kidneys. These observations suggest that oxamide-stone formation was initiated not by tubular necrosis produced by the toxic action of oxalate on the tubules, but rather by mechanical obstruction of the tubules.