Tissue kallikrein, blood pressure regulation, and hypertension: insight from genetic kallikrein deficiency

2013 ◽  
Vol 394 (3) ◽  
pp. 329-333 ◽  
Author(s):  
Louis Potier ◽  
Ludovic Waeckel ◽  
Christine Richer ◽  
Ronan Roussel ◽  
Nadine Bouby ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Regulation ◽  
Genetic Models ◽  
Tissue Kallikrein ◽  
Sodium Retention ◽  
Pressure Regulation ◽  
Blood Pressure Elevation ◽  
Genetic Deficiency ◽  
Kallikrein Activity ◽  
Deficient Mice

Abstract Tissue kallikrein has been suggested to be involved in blood pressure regulation and in protection against hypertension. However, this hypothesis remains debated. Recently, murine genetic models of kallikrein deficiency have been engineered and partial genetic deficiency in kallikrein activity has been characterized in humans. Studies in kallikrein-deficient mice indicate that kallikrein indeed influences blood pressure in the setting of mineralocorticoid excess and salt retention but not in normotensive animals and in high renin hypertension. These observations suggest that kallikrein can have antihypertensive function in physiological situations where sodium retention can trigger blood pressure elevation.

scholarly journals Insulin and Blood Pressure Regulation : Role of Sodium Retention and Sympathetic Nervous System

1993 ◽  
Vol 57 (supplementIV) ◽  
pp. 1154-1156
Author(s):  
Toshio Kushiro ◽  
Hirofumi Tomiyama ◽  
Katsuo Kanmatsuse ◽  
Nagao Kajiwara
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Blood Pressure Regulation ◽  
Sodium Retention ◽  
Pressure Regulation ◽  
Sympathetic Nervous

scholarly journals ACE2 and ADAM17 Interaction Regulates the Activity of Presympathetic Neurons

Hypertension ◽  
2019 ◽  
Vol 74 (5) ◽  
pp. 1181-1191 ◽  
Author(s):  
Snigdha Mukerjee ◽  
Hong Gao ◽  
Jiaxi Xu ◽  
Ryosuke Sato ◽  
Andrea Zsombok ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Paraventricular Nucleus ◽  
Renin Angiotensin System ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Neurogenic Hypertension ◽  
Blood Pressure Elevation ◽  
Angiotensin System ◽  
Renin Angiotensin

Brain renin angiotensin system within the paraventricular nucleus plays a critical role in balancing excitatory and inhibitory inputs to modulate sympathetic output and blood pressure regulation. We previously identified ACE2 and ADAM17 as a compensatory enzyme and a sheddase, respectively, involved in brain renin angiotensin system regulation. Here, we investigated the opposing contribution of ACE2 and ADAM17 to hypothalamic presympathetic activity and ultimately neurogenic hypertension. New mouse models were generated where ACE2 and ADAM17 were selectively knocked down from all neurons (AC-N) or Sim1 neurons (SAT), respectively. Neuronal ACE2 deletion revealed a reduction of inhibitory inputs to AC-N presympathetic neurons relevant to blood pressure regulation. Primary neuron cultures confirmed ACE2 expression on GABAergic neurons synapsing onto excitatory neurons within the hypothalamus but not on glutamatergic neurons. ADAM17 expression was shown to colocalize with angiotensin-II type 1 receptors on Sim1 neurons, and the pressor relevance of this neuronal population was demonstrated by photoactivation. Selective knockdown of ADAM17 was associated with a reduction of FosB gene expression, increased vagal tone, and prevented the acute pressor response to centrally administered angiotensin-II. Chronically, SAT mice exhibited a blunted blood pressure elevation and preserved ACE2 activity during development of salt-sensitive hypertension. Bicuculline injection in those models confirmed the supporting role of ACE2 on GABAergic tone to the paraventricular nucleus. Together, our study demonstrates the contrasting impact of ACE2 and ADAM17 on neuronal excitability of presympathetic neurons within the paraventricular nucleus and the consequences of this mutual regulation in the context of neurogenic hypertension.

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