Increase in Vascular Sensitivity to Angiotensin II and Norepinephrine after Four-Day Infusion of 0.3 M Sodium Chloride in Conscious Kininogen-Deficient Brown Norway Katholiek Rats

Murakami, Masataka; Adachi, Kai; Kuribayashi, Yoshikazu; Mizogami, Susumu; Katori, Makoto

doi:10.1254/jjp.69.149

Cited by 19 publications

(16 citation statements)

References 20 publications

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“…18). The arterio lar sensitivity to norepinephrine also increased 30-fold (200). The sensitivity of the arterioles of normal BN-Ki rats was not changed after infusion of either 0.15 or 0.3 M NaC1 solution.…”

Section: Genetic Backgroundmentioning

confidence: 81%

“…Importance of sodium accumulation and increased vascular sensitivity in induction of hypertension Low sodium loading or angiotensin II infusion in mutant BN-Ka rats increases the circulating blood volume with sodium retention, since the hematocrit value in deficient BN-Ka rats was decreased during angiotensin in fusion, whereas no difference in hematocrit was observed after a similar infusion in normal BN-Ki rats (198). However, the following experiments (200) indicate that sodium accumulation plays a crucial role in the develop ment of hypertension.…”

Section: Genetic Backgroundmentioning

confidence: 88%

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Pivotal Role of Renal Kallikrein-Kinin System in the Development of Hypertension and Approaches to New Drugs Based on This Relationship

Katori

Murakami

1996

Japanese Journal of Pharmacology

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ABSTRACT-Renal kallikrein is one of the tissue kallikreins, and the distal nephron is fully equipped as an element of the kallikrein-kinin system. Although a low excretion of urinary kallikrein has been reported in essential hypertension, the results from studies on patients with hypertension are not consistent. Congeni tally hypertensive animals also excrete lowered levels of urinary kallikrein, but the effects of this are yet unknown. Extensive genetic and environmental studies on large Utah pedigrees suggest that the causes of hypertension are closely related to the combination of low kallikrein excretion and the potassium intake. Mutant kininogen-deficient Brown Norway-Katholiek rats, which cannot generate kinin in the urine, are very sensitive to salt loading and to sodium retention by aldosterone released by a non-pressor dose of angiotensin II, which results in hypertension. The major function of renal kallikrein-kinin system is to excrete sodium and water when excess sodium is present in the body. Failure of this function causes accumulation of sodium in the cerebrospinal fluid and erythrocytes, and probably in the vascular smooth muscle, which become sensitive to vasoconstrictors. We hypothesize that impaired function of the renal kallikrein-kinin system may play a pivotal role in the early development of hypertension. Inhibitors of kinin degradation in renal tubules and agents, which accelerate the secretion of urinary kallikrein from the con necting tubules and increase the generation of urinary kinin, may be novel drugs against hypertension.

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Section: Genetic Backgroundmentioning

confidence: 81%

Section: Genetic Backgroundmentioning

confidence: 88%

Pivotal Role of Renal Kallikrein-Kinin System in the Development of Hypertension and Approaches to New Drugs Based on This Relationship

Katori

Murakami

1996

Japanese Journal of Pharmacology

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“…Concomitant increases were observed in the sodium levels not only in the serum, but also in the erythrocytes and in the CSF (64). The dose-response curve of the arterioles for angiotensin II in the kininogen-deficient BN-Ka rats shifted to the left (10-fold increase) after infusion of 0.3 M NaCl, and the arteriolar sensitivity to norepinephrine also increased by a factor of 30 (64). In contrast, the sensitivity of the arterioles of normal BN-Ki rats to angiotensin II and norepinephrine did not change after the infusion of either 0.15 or 0.3 M NaCl.…”

Section: ) Increase In the Arteriolar Sensitivity To Vasopressor Submentioning

confidence: 94%

“…In contrast, infusion of NaCl solution of twice the concentration (0.3 M) of NaCl solution into the deficient BN-Ka rats significantly increased the mean arterial pressure to 127 ± 3 mmHg (P<0.05) one day after the start of infusion. Concomitant increases were observed in the sodium levels not only in the serum, but also in the erythrocytes and in the CSF (64). The dose-response curve of the arterioles for angiotensin II in the kininogen-deficient BN-Ka rats shifted to the left (10-fold increase) after infusion of 0.3 M NaCl, and the arteriolar sensitivity to norepinephrine also increased by a factor of 30 (64).…”

Section: ) Increase In the Arteriolar Sensitivity To Vasopressor Submentioning

confidence: 96%

A Missing Link Between a High Salt Intake and Blood Pressure Increase

Katori

Murakami

2006

J Pharmacol Sci

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Abstract. It is widely accepted that a high sodium intake triggers blood pressure rise. However, only one-third of the normotensive subjects were reported to show salt-sensitivity in their blood pressure. Many factors have been proposed as causes of salt-sensitive hypertension, but none of them provides a satisfactory explanation. We propose, on the basis of accumulated data, that the reduced activity of the kallikrein-kinin system in the kidney may provide this link. Renal kallikrein is secreted by the distal connecting tubular cells and all kallikrein-kinin system components are distributed along the collecting ducts in the distal nephron. Bradykinin generated is immediately destroyed by carboxypeptidase Y-like exopeptidase and neutral endopeptidase, both quite independent from the kininases in plasma, such as angiotensin converting enzyme. The salt-sensitivity of the blood pressure depends largely upon ethnicity and potassium intake. Interestingly, potassium and ATP-sensitive potassium (K ATP ) channel blockers accelerate renal kallikrein secretion and suppress blood pressure rises in animal hypertension models. Measurement of urinary kallikrein may become necessary in salt-sensitive normotensive and hypertensive subjects. Furthermore, pharmaceutical development of renal kallikrein releasers, such as K ATP channel blockers, and renal kininase inhibitors, such as ebelactone B, may lead to the development of novel antihypertensive drugs.

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“…10,12 It is important that sodium accumulation in the cells caused a 10-fold and a 30-fold increase in vascular sensitivity to angiotensin II and epinephrine, respectively. 13 Consequently, a dysfunction of the renal kallikrein-kinin system leads to salt sensitivity in rats.…”

Section: Introductionmentioning

confidence: 99%

An ATP-sensitive potassium channel blocker suppresses sodium-induced hypertension through increased secretion of urinary kallikrein

et al. 2009

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It is suggested that an ATP-sensitive potassium channel blocker suppresses sodium-induced hypertension through increased secretion of urinary kallikrein. We reported that glibenclamide, an ATP-sensitive potassium channel blocker, accelerated dose-dependent secretion of renal kallikrein in sliced kidney cortex and in vivo in rats. In vehicle-treated normal BrownNorway-Kitasato (nBN-Ki) rats, the administration of glibenclamide increased urinary kallikrein secretion, but changed neither the systolic blood pressure nor the urinary sodium on low (0.3%) NaCl diets. Although on high (8%) NaCl diets, the systolic blood pressure of the nBN-Ki rats administrated glibenclamide was significantly lower (Po0.05). The urinary levels of kallikrein and sodium of the nBN-Ki rats administrated glibenclamide were significantly increased (Po0.05, glibenclamide vs. vehicle). A similar result was obtained with a kidney-selective ATP-sensitive potassium blocker, N,N¢-dicyclohexyl-4-morpholinecarboxamidine (U18177), in SD rats. Mutant kininogen-deficient Brown-Norway Katholiek (muBN-Ka) rats fed high (8%) NaCl diets showed an increase in urinary kallikrein levels, but showed neither hypotensive nor natriuretic actions by glibenclamide. A bradykinin B 2 receptor antagonist,-dichlorobenzyloxy]-2-methylquinoline (FR173657), which was administrated to SD rats, together with glibenclamide, abolished the hypotensive and natriuretic effects of glibenclamide in high-sodium (8%NaCl) hypertension, despite an accelerated secretion of urinary kallikrein. Therefore, these results indicate that glibenclamide, an ATP-sensitive potassium channel blocker suppressed sodium-induced hypertension through sodium excretion from the kidney resulting from accelerated secretion of urinary kallikrein.

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Increase in Vascular Sensitivity to Angiotensin II and Norepinephrine after Four-Day Infusion of 0.3 M Sodium Chloride in Conscious Kininogen-Deficient Brown Norway Katholiek Rats

Cited by 19 publications

References 20 publications

Pivotal Role of Renal Kallikrein-Kinin System in the Development of Hypertension and Approaches to New Drugs Based on This Relationship

Pivotal Role of Renal Kallikrein-Kinin System in the Development of Hypertension and Approaches to New Drugs Based on This Relationship

A Missing Link Between a High Salt Intake and Blood Pressure Increase

An ATP-sensitive potassium channel blocker suppresses sodium-induced hypertension through increased secretion of urinary kallikrein

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