Renal (Tissue) Kallikrein-Kinin System in the Kidney and Novel Potential Drugs for Salt-Sensitive Hypertension

Kikuchi, Makoto; Murakami, Masataka

doi:10.1007/978-3-319-06683-7_4

Cited by 11 publications

(18 citation statements)

References 228 publications

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“…1-6 Bradykinin is the most biologically active peptide of KKS and acts mainly as a local hormone by activating specific G protein coupled receptors, known as B 1 and B 2 receptors (B 1 R and B 2 R), with most of the cardiovascular effects being mediated by the B 2 R. 2-6 The B 2 R protein is constitutively expressed in most tissues and over-expression of B 2 R causes hypotension in transgenic mice. 7 Vascular endothelial cells express B 2 R abundantly, where it is functionally linked to activation of endothelial nitric oxide (NO) synthase.…”

Section: Introductionmentioning

confidence: 99%

“…Expression of B 1 R is minimal under normal circumstances, but is induced by inflammation and organ damage. 3,6,8 Furthermore, the B 2 R forms a complex with angiotensin converting enzyme, and this is thought to play a role in cross-talk between the renin-angiotensin system (RAS) and KKS. 3,6,9 The integrative role of KKS is further supported by involvement of B 2 R activation in renin and NO release.…”

Section: Introductionmentioning

confidence: 99%

“…3,6,8 Furthermore, the B 2 R forms a complex with angiotensin converting enzyme, and this is thought to play a role in cross-talk between the renin-angiotensin system (RAS) and KKS. 3,6,9 The integrative role of KKS is further supported by involvement of B 2 R activation in renin and NO release. 6,10-12 These interactions may significantly contribute to the regulation of kidney function.…”

Section: Introductionmentioning

confidence: 99%

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Conditional knockout of collecting duct bradykinin B₂receptors exacerbates angiotensin II-induced hypertension during high salt intake

Kopkan

Husková

Jíchová

et al. 2015

Clinical and Experimental Hypertension

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We elucidated the role of collecting duct kinin B2 receptor (B2R) in the development of salt-sensitivity and angiotensin II (ANG II)-induced hypertension. To this end, we used a Cre-Lox recombination strategy to generate mice lacking Bdkrb2 gene for B2R in the collecting duct (Hoxb7-Cretg/+:Bdkrb2flox/flox). In 3 groups of control (Bdkrb2flox/flox) and 3 groups of UBBdkrb2−/− mice, systolic blood pressure (SBP) responses to high salt intake (4 or 8% NaCl; HS) were monitored by radiotelemetry in comparison with standard salt diet (0.4% NaCl) prior to and during subcutaneous ANG II infusion (1000 ng/min/kg) via osmotic minipumps. High salt intakes alone for 2 weeks did not alter SBP in either strain. ANG II significantly increased SBP equally in control (121 ± 2 to 156 ± 3 mmHg) and UBBdkrb2−/− mice (120 ± 2 to 153 ± 2 mmHg). The development of ANG II-induced hypertension was exacerbated by 4%HS in both control (125 ± 3 to 164 ± 5 mmHg) and UBBdkrb2−/− mice (124 ± 2 to 162 ± 3 mmHg) during 2 weeks. Interestingly 8%HS caused a more profound and earlier ANG II-induced hypertension in UBBdkrb2−/− (129 ± 2 to 166 ± 3 mmHg) as compared to control (128 ± 2 to 158 ± 2 mmHg) and it was accompanied by body weight loss and increased mortality. In conclusion, targeted inactivation of B2R in the renal collecting duct does not cause salt-sensitivity; however, collecting duct B2R attenuates the hypertensive actions of ANG II action under conditions of very high salt intake.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Conditional knockout of collecting duct bradykinin B₂receptors exacerbates angiotensin II-induced hypertension during high salt intake

Kopkan

Husková

Jíchová

et al. 2015

Clinical and Experimental Hypertension

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“…More recent family studies have suggested that individuals with a greater urinary kallikrein excretion genotype were less likely to have one or two hypertensive parents and urinary kallikrein was recognized as a strong marker of a genetic component of essential hypertension [ 106 , 107 ]. More recent data have suggested that the renal kallikrein-kinin system participates in the development of salt-sensitive hypertension and pharmacological interventions of this renal system may be a new pathway to lower BP in some individuals with hypertension [ 108 ].…”

Section: Kininsmentioning

confidence: 99%

Pathophysiology of Hypertension

Burnier

Wuerzner

2015

Pathophysiology and Pharmacotherapy of Cardiovascular Disease

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Hypertension is a rather simple phenotype characterized by an increase in systemic blood pressure above an arbitrarily defi ned threshold. Yet, the mechanisms leading to the increase in blood pressure are extremely complex and involved a wide variety of neurohormonal, renal, metabolic, and vascular factors. The causes of hypertension differ substantially in young children, in middle-aged men and women, and in the elderly. In children, hypertension is often the appearance of a renal or endocrine disease, whereas in adults, the large majority of patients with hypertension have an essential hypertension, a denomination refl ecting that the mechanisms are not fully understood although some well-defi ned pathogenic factors have been described in patients with hypertension associated with diabetes mellitus, obesity, hyperaldosteronism, renovascular hypertension, or renal diseases. In the elderly, hypertension is strongly associated with factors leading to vascular aging and loss of arterial elasticity. The purpose of this chapter is to review the pathophysiology of hypertension in these different clinical situations in light of the recent literature.

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“…Bradykinin synthesis is protective against hypertensive renal damage and diabetic nephropathy [65,66]. Studies of the selective kinases ebelactone B and poststatin indicate promise as novel antihypertensive agents [67]. Bradykinin’s actions are prolonged by the use of ACE inhibitors, with potentiation of renal bradykinin a potential advantageous therapeutic effect of the ACE inhibitors, in addition to a cause of angioedema [68].…”

Section: Bradykininmentioning

confidence: 99%

Kidney tubules

Ferenbach

Bonventre

2016

Current Opinion in Nephrology and Hypertension

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Purpose of review The kidney mediates the excretion or conservation of water and electrolytes in the face of changing fluid and salt intake and losses. To ultrafilter and reabsorb the exact quantities of free water and salts to maintain euvolemia a range of endocrine, paracrine, and hormonal signaling systems have evolved linking the tubules, capillaries, glomeruli, arterioles, and other intrinsic cells of the kidney. Our understanding of these systems remains incomplete. Recent findings Recent work has provided new insights into the workings of the communication pathways between tubular segments and the glomeruli and vasculature, with novel therapeutic agents in development. Particular progress has also been made in the visualization of tubuloglomerular feedback. Summary The review summarizes our current understanding of pathway functions in health and disease, as well as future therapeutic options to protect the healthy and injured kidney.

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Renal (Tissue) Kallikrein-Kinin System in the Kidney and Novel Potential Drugs for Salt-Sensitive Hypertension

Cited by 11 publications

References 228 publications

Conditional knockout of collecting duct bradykinin B₂receptors exacerbates angiotensin II-induced hypertension during high salt intake

Conditional knockout of collecting duct bradykinin B₂receptors exacerbates angiotensin II-induced hypertension during high salt intake

Pathophysiology of Hypertension

Kidney tubules

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Renal (Tissue) Kallikrein-Kinin System in the Kidney and Novel Potential Drugs for Salt-Sensitive Hypertension

Cited by 11 publications

References 228 publications

Conditional knockout of collecting duct bradykinin B2receptors exacerbates angiotensin II-induced hypertension during high salt intake

Conditional knockout of collecting duct bradykinin B2receptors exacerbates angiotensin II-induced hypertension during high salt intake

Pathophysiology of Hypertension

Kidney tubules

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Product

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Conditional knockout of collecting duct bradykinin B₂receptors exacerbates angiotensin II-induced hypertension during high salt intake

Conditional knockout of collecting duct bradykinin B₂receptors exacerbates angiotensin II-induced hypertension during high salt intake