Pendrin localizes to the adrenal medulla and modulates catecholamine release

Pendrin ( Slc26a4) is a Cl−/HCO3− exchanger expressed in renal intercalated cells and mediates renal Cl− absorption. With pendrin gene ablation, blood pressure and vascular volume fall, which increases plasma renin concentration. However, serum aldosterone does not significantly increase in pendrin-null mice, suggesting that pendrin regulates adrenal zona glomerulosa aldosterone production. Therefore, we examined pendrin expression in the adrenal gland using PCR, immunoblots, and immunohistochemistry. Pendrin protein was detected in adrenal lysates from wild-type but not pendrin-null mice. However, immunohistochemistry and qPCR of microdissected adrenal zones showed that pendrin was expressed in the adrenal medulla, rather than in cortex. Within the adrenal medulla, pendrin localizes to both epinephrine- and norepinephrine-producing chromaffin cells. Therefore, we examined plasma catecholamine concentration and blood pressure in wild-type and pendrin-null mice under basal conditions and then after 5 and 20 min of immobilization stress. Under basal conditions, blood pressure was lower in the mutant than in the wild-type mice, although epinephrine and norepinephrine concentrations were similar. Catecholamine concentration and blood pressure increased markedly in both groups with stress. With 20 min of immobilization stress, epinephrine and norepinephrine concentrations increased more in pendrin-null than in wild-type mice, although stress produced a similar increase in blood pressure in both groups. We conclude that pendrin is expressed in the adrenal medulla, where it blunts stress-induced catecholamine release.

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Hormonal changes associated with hypertension in neoplasia-induced hypercalcemia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1982.242.5.e330 ◽

1982 ◽

Vol 242 (5) ◽

pp. E330-E334 ◽

Cited By ~ 2

Author(s):

J. R. Sowers ◽

J. D. Barrett

Keyword(s):

Blood Pressure ◽

Systolic Blood Pressure ◽

Immobilization Stress ◽

Systolic Pressure ◽

Plasma Renin ◽

Cell Tumor ◽

Plasma Catecholamine ◽

Hormonal Changes ◽

Tumor Transplantation ◽

Vasoactive Hormones

Neoplasia-induced hypercalcemia in the Fischer rat results in hypertension 1 wk after Leydig cell tumor transplantation. Systolic blood pressure, plasma catecholamine, prolactin, plasma renin activity (PRA), and aldosterone responses to immobilization stress were evaluated in Fischer rats 10 days after tumor transplantation and in age-matched nontransplanted controls. Basal systolic blood pressure, norepinephrine, and PRA levels at 10 days after tumor transplantation were higher in association with elevated calcium levels in tumor-transplanted rats than in controls. Systolic pressure, norepinephrine, and epinephrine responses to immobilization stress were greater in the hypercalcemia 10-day transplanted rats. Although basal levels of prolactin and aldosterone were similar in the two groups. These observations suggest that elevated levels of the vasoactive hormones norepinephrine and angiotensin may play a pivotal role in development of hypertension in association with neoplasia-induced hypercalcemia. Further, neoplasia-induced hypercalcemia in the Fischer rat is associated with a relative hyperreninemic hypoaldosteronism state.

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Salt sensitivity of blood pressure in NKCC1-deficient mice

AJP Renal Physiology ◽

10.1152/ajprenal.90392.2008 ◽

2008 ◽

Vol 295 (4) ◽

pp. F1230-F1238 ◽

Cited By ~ 40

Author(s):

Soo Mi Kim ◽

Christoph Eisner ◽

Robert Faulhaber-Walter ◽

Diane Mizel ◽

Susan M. Wall ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Wheel Running ◽

Plasma Renin ◽

Pressure Change ◽

Standard Diet ◽

Wild Type ◽

Vascular Effects ◽

Arterial Blood ◽

Deficient Mice

NKCC1 is a widely expressed isoform of the Na-2Cl-K cotransporter that mediates several direct and indirect vascular effects and regulates expression and release of renin. In this study, we used NKCC1-deficient (NKCC1−/−) and wild-type (WT) mice to assess day/night differences of blood pressure (BP), locomotor activity, and renin release and to study the effects of high (8%) or low (0.03%) dietary NaCl intake on BP, activity, and the renin/aldosterone system. On a standard diet, 24-h mean arterial blood pressure (MAP) and heart rate determined by radiotelemetry, and their day/night differences, were not different in NKCC1−/− and WT mice. Spontaneous and wheel-running activities in the active night phase were lower in NKCC1−/− than WT mice. In NKCC1−/− mice on a high-NaCl diet, MAP increased by 10 mmHg in the night without changes in heart rate. In contrast, there was no salt-dependent blood pressure change in WT mice. MAP reductions by hydralazine (1 mg/kg) or isoproterenol (10 μg/mouse) were significantly greater in NKCC1−/− than WT mice. Plasma renin (PRC; ng ANG I·ml−1·h−1) and aldosterone (aldo; pg/ml) concentrations were higher in NKCC1−/− than WT mice (PRC: 3,745 ± 377 vs. 1,245 ± 364; aldo: 763 ± 136 vs. 327 ± 98). Hyperreninism and hyperaldosteronism were found in NKCC1−/− mice during both day and night. High Na suppressed PRC and aldosterone in both NKCC1−/− and WT mice, whereas a low-Na diet increased PRC and aldosterone in WT but not NKCC1−/− mice. We conclude that 24-h MAP and MAP circadian rhythms do not differ between NKCC1−/− and WT mice on a standard diet, probably reflecting a balance between anti- and prohypertensive factors, but that blood pressure of NKCC1−/− mice is more sensitive to increases and decreases of Na intake.

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Effects of nonhypotensive endotoxemia in conscious rats: role of prostaglandins

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1988.254.3.h509 ◽

1988 ◽

Vol 254 (3) ◽

pp. H509-H516 ◽

Cited By ~ 3

Author(s):

M. Burnier ◽

B. Waeber ◽

J. F. Aubert ◽

J. Nussberger ◽

H. R. Brunner

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Plasma Renin Activity ◽

Renal Blood Flow ◽

Plasma Renin ◽

Renin Activity ◽

Plasma Norepinephrine ◽

Plasma Catecholamine ◽

Conscious Rats

A nonhypotensive dose of endotoxin was administered to normal conscious rats to evaluate the vascular and humoral effects of endotoxemia per se. Mean blood pressure and heart rate remained stable during the 45 min infusion of Escherichia coli endotoxin (0.01 mg/min). However, a marked increase in plasma renin activity (4.2 +/- 0.48 vs. 30.2 +/- 6 ng.ml-1.h-1, mean +/- SE, P less than 0.01), plasma epinephrine (0.112 +/- 0.04 vs. 1.71 +/- 0.5 ng/ml, P less than 0.01), and plasma norepinephrine (0.269 +/- 0.028 vs. 1.3 +/- 0.2 ng/ml, P less than 0.001) was observed during infusion in endotoxin-treated rats when compared with the vehicle-treated animals. In addition, the blood pressure response to exogenous norepinephrine was significantly reduced during nonhypotensive endotoxemia. Significant changes in regional blood flow distribution, as assessed by radiolabeled microspheres, were observed in endotoxemic rats; in particular a decrease in renal blood flow (7.39 +/- 0.43 vs. 5.97 +/- 0.4 ml.min-1.g-1, P less than 0.05) and an increase in coronary blood flow (5.01 +/- 0.38 vs. 6.44 +/- 0.33 ml.min-1.g-1, P less than 0.01) were found. The role of prostaglandins in the vascular and humoral alterations induced by nonhypotensive endotoxemia was also examined. Pretreatment with indomethacin (5 mg) prevented the increase in plasma renin activity as well as plasma catecholamine levels. On the contrary, the decreased vascular reactivity and the reduction in renal blood flow observed during endotoxemia were not affected by prostaglandin synthesis inhibition. Thus significant vascular and humoral changes have been found during endotoxemia even in absence of hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hypotension in NKCC1 null mice: role of the kidneys

AJP Renal Physiology ◽

10.1152/ajprenal.00309.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. F409-F416 ◽

Cited By ~ 58

Author(s):

Susan M. Wall ◽

Mark A. Knepper ◽

Kathryn A. Hassell ◽

Michael P. Fischer ◽

Adetola Shodeinde ◽

...

Keyword(s):

Blood Pressure ◽

Kidney Tissue ◽

Free Water ◽

Plasma Renin ◽

Wild Type ◽

Deficient Diet ◽

Water Excretion ◽

Α Subunit ◽

Serum Aldosterone ◽

Transporter Expression

NKCC1 null mice are hypotensive, in part, from the absence of NKCC1-mediated vasoconstriction. Whether these mice have renal defects in NaCl and water handling which contribute to the hypotension is unexplored. Therefore, we asked 1) whether NKCC1 ( −/−) mice have a defect in the regulation of NaCl and water balance, which might contribute to the observed hypotension and 2) whether the hypotension observed in these mice is accompanied by endocrine abnormalities and/or downregulation of renal Na+ transporter expression. Thus we performed balance studies, semiquantitative immunoblotting, and immunohistochemistry of kidney tissue from NKCC1 ( +/+) and NKCC1 ( −/−) mice which consumed either a high (2.8% NaCl)- or a low-NaCl (0.01% NaCl) diet for 7 days. Blood pressure was lower in NKCC1 ( −/−) than NKCC1 ( +/+) mice following either high or low dietary NaCl intake. Relative to wild-type mice, NKCC1 null mice had a lower plasma ANP concentration, a higher plasma renin and a higher serum K+ concentration with inappropriately low urinary K+ excretion, although serum aldosterone was either the same or only slightly increased in the mutant mice. Expression of NHE3, the α-subunit of the Na-K-ATPase, NCC, and NKCC2 were higher in NKCC1 null than in wild-type mice, although differences were generally greater during NaCl restriction. NKCC1 null mice had a reduced capacity to excrete free water than wild-type mice, which resulted in hypochloremia following the NaCl-deficient diet. Hypochloremia did not occur from increased aquaporin-1 (AQP1) or 2 protein expression or from redistribution of AQP2 to the apical regions of principal cells. Instead, NKCC1 null mice had a blunted increase in urinary osmolality following vasopressin administration, which should increase free water excretion and attenuate the hypochloremia. In conclusion, aldosterone release is inappropriately low in NKCC1 null mice. Moreover, the action of aldosterone and vasopressin is altered within kidneys of NKCC1 null mice, which likely contributes to their hypotension. Increased Na+ transporter expression, increased plasma renin, and reduced plasma ANP, as observed in NKCC1 null mice, should increase vascular volume and blood pressure, thus minimizing hypotension.

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Natriuretic peptides buffer renin-dependent hypertension

AJP Renal Physiology ◽

10.1152/ajprenal.00668.2013 ◽

2014 ◽

Vol 306 (12) ◽

pp. F1489-F1498 ◽

Cited By ~ 14

Author(s):

Theo Demerath ◽

Janina Staffel ◽

Andrea Schreiber ◽

Daniela Valletta ◽

Frank Schweda

Keyword(s):

Blood Pressure ◽

Renovascular Hypertension ◽

Natriuretic Peptide ◽

Natriuretic Peptides ◽

Plasma Renin ◽

Control Mechanisms ◽

Wild Type ◽

Renal Vasoconstriction ◽

Arterial Blood ◽

Independent Effects

The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP−/−) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP−/− mice were hypertensive and had reduced PRC compared with that in wild-type ANP+/+ mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP−/− mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A−/− mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A+/+ mice. However, the higher blood pressure in GC-A−/− mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A−/− mice than in GC-A+/+ mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II.

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Angiotensin II-mediated catecholamine release during the pressor response in rats

Journal of Endocrinology ◽

10.1677/joe.0.1420019 ◽

1994 ◽

Vol 142 (1) ◽

pp. 19-28 ◽

Cited By ~ 15

Author(s):

D G Butler ◽

D A Butt ◽

D Puskas ◽

G Y Oudit

Keyword(s):

Angiotensin Ii ◽

Pressor Response ◽

Plasma Renin ◽

Sympathetic Nerves ◽

Catecholamine Release ◽

Plasma Catecholamine ◽

Ang Ii ◽

Sprague Dawley ◽

Pressor Responses ◽

Plasma Catecholamine Concentrations

Abstract Angiotensin II (ANG II)-mediated catecholamine release and its possible contribution to the pressor response was assessed in baroreceptor-denervated rats. Neonatal male Sprague-Dawley rats were injected with the sympatholytic drug, guanethidine monosulphate (50 mg/kg s.c., 6 days/week) for 40 days. Plasma catecholamine concentrations were measured using a 3H-radioenzymatic assay as follows: (a) before and 30 s after the injection of saline or ANG II (79·3 pmol/kg i.v.), at the peak of the pressor response, then 50 s and 80 s thereafter, in guanethidine-treated (GUAN) and saline-injected (SHAM) rats, and (b) before and after adrenalectomy (ADX), following the same time-sequence for ANG II as in (a). Peak pressor responses to graded doses of ANG II (6·6, 26·4, 53·0 and 79·3 pmol/kg i.v.) were measured in GUAN+ADX and ADX rats. Destruction of peripheral sympathetic nerves was confirmed by measurements of plasma noradrenaline (NA), adrenaline (AD) and dopamine (DA) concentrations and by changes in pressor responses and heart rates following i.v. doses of tyramine. ANG II induced significantly (P<0·05) greater pressor responses in GUAN+ADX rats than in ADX rats, especially after the 53·0 and 79·3 pmol/kg doses. Plasma AD concentrations increased within seconds after the pressor response to ANG II in both GUAN and SHAM rats but there was no change in plasma NA or DA concentrations (P<0·05). ANG-II-mediated AD release from the adrenal medulla may contribute to the overall pressor action of the peptide. The vasculature became more sensitive to ANG II at a time when NA and DA depletion occurred following sympathectomy and/or adrenalectomy. This heightened sensitivity to ANG II was not due to a decrease in circulating ANG II in sympathectomized rats because even though plasma renin activity fell from 6·54 ±0·52 to 3·77 ±0·26 ng ANG I/ml per h it remained within the normal range. Journal of Endocrinology (1994) 142, 19–28

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Adrenomedullary origin of the hindquarter vasodilation during the transposition response of the rat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y88-003 ◽

1988 ◽

Vol 66 (1) ◽

pp. 18-21

Author(s):

S. Sakata ◽

J. Iriuchijima

Keyword(s):

Blood Flow ◽

Adrenal Medulla ◽

Home Cage ◽

Cardiovascular Response ◽

Systemic Arterial Pressure ◽

Plasma Catecholamine ◽

Plasma Adrenaline ◽

Arterial Blood ◽

Radioenzymatic Assay ◽

Catecholamine Concentration

Transposing a rat from the home cage to a new cage produces a cardiovascular response (transposition response) characterized by an increase in hindquarter blood flow with unchanged systemic arterial pressure. Arterial blood samples were collected from rats before and during this response for radioenzymatic assay of catecholamines. During the transposition response, the concentration of adrenaline and noradrenaline in plasma increased about six- and two-fold, respectively. Ablation of the adrenal medulla prevented these changes in plasma catecholamine concentration. Constant i.v. infusion of adrenaline, at rates producing a hindquarter flow approximately matching that observed during the transposition response, evoked an increase in plasma adrenaline concentration also approximately matching the increase observed during the transposition response. It is concluded that the increase in plasma adrenaline secreted from the adrenal medulla is the main cause of the increase in hindquarter blood flow in the transposition response.

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Abstract MP09: Adrenal-specific Deletion of TASK Channels Evokes Normal-Renin Hypertension

Hypertension ◽

10.1161/hyp.66.suppl_1.mp09 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Nick A Guagliardo ◽

Thu H Le ◽

Douglas A Bayliss ◽

David T Breault ◽

Paula Q Barrett

Keyword(s):

Blood Pressure ◽

Radio Telemetry ◽

Plasma Renin ◽

Zona Glomerulosa ◽

Angiotensin Ii Receptor ◽

Task Channels ◽

The Difference ◽

Angiotensin Ii Receptor Blockade ◽

Design And Methods ◽

Specific Deletion

Objectives: Dysregulation of aldosterone (Aldo) production is predicted to evoke major features of idiopathic primary hyperaldosteronism (IHA): low renin, elevated blood pressure and suppressed control by high Na. We have previously demonstrated in mice that global deletion of background TWIK-related acid-sensitive K (TASK) channels (TASK-1, TASK-3) effect a ~20mV decrease in the membrane potential of Zona Glomerulosa (ZG) cells to produce frank autonomous overproduction of Aldo, low renin, and hypertension (HT), mimicking the salient features of human IHA. In the current study, we ask if specific deletion of TASK channels in ZG cells is sufficient to produce hyperaldosteronism and the predicted sequela or if extra-adrenal deletion of TASK channels is required. Design and Methods: We generated a trigenic mouse-line ( AS +Cre ::TASK-1 ff ::TASK-3 ff , zT1T3KO) in which TASK-1 and TASK-3 subunits were specifically deleted in ZG cells. The renin-angiotensin-aldosterone system (RAAS) was evaluated in mice housed in metabolic cages and stabilized on various salt diets. Urinary Aldo concentration was measured and normalized to creatinine (ng Aldo/mg creatinine; 24 hr. urine collection). Blood pressure was recorded in conscious, freely moving mice using radio telemetry, and plasma renin concentration was measured from tail vein sampling. Results: Overproduction of aldosterone on normal-salt diet (0.3% Na) was modest in zT1T3KO mice compared to littermate controls (WT; WT 9.4; KO 11.8 ng/mg, 1.25-fold). Suppression of Aldo production by high-salt (2% Na) was blunted, exaggerating the difference in Aldo production between genotypes (WT 3.0; KO 7.4 ng/mg, 2.43-fold). zT1T3KO mice were hypertensive (mean MAP: WT 103.5; KO 113.1 mmHg), yet renin levels remained normal. Neither hyperaldosteronism nor HT could be corrected by angiotensin II receptor blockade, suggesting overproduction of Aldo and HT are independent of RAAS. Conclusions: Limiting TASK deletion to ZG cells results in normal renin HT driven by modest autonomous hyperaldosteronism, a stark contrast to the phenotypic features of IHA recapitulated by global TASK deletion. Together these mouse models provide insight into the role of ZG- vs extra-adrenal-dysfunction in the pathology of IHA.

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Blood pressure regulation during hypotension in two teleost species: differential involvement of the renin-angiotensin and adrenergic systems

Journal of Experimental Biology ◽

10.1242/jeb.202.12.1677 ◽

1999 ◽

Vol 202 (12) ◽

pp. 1677-1690 ◽

Cited By ~ 3

Author(s):

N.J. Bernier ◽

J.E. Mckendry ◽

S.F. Perry

Keyword(s):

Blood Pressure ◽

Renin Angiotensin System ◽

Catecholamine Release ◽

Adrenergic Nerves ◽

Plasma Catecholamine ◽

Ang Ii ◽

Angiotensin System ◽

Renin Angiotensin ◽

Plasma Catecholamine Concentrations

The stimulatory effects of angiotensin II (Ang II) on catecholamine release and the contributions of the renin-angiotensin system, humoral catecholamines and adrenergic nerves to blood pressure regulation were investigated in rainbow trout (Oncorhynchus mykiss) and American eel (Anguilla rostrata). In trout, bolus injections of homologous [Asn1,Val5]-Ang II (100 or 500 pmol kg-1) increased catecholamine secretion rates and plasma catecholamine concentrations from in situ posterior cardinal vein preparations and chronically cannulated fish, respectively. In contrast, in situ or in vivo injections of similar doses of Ang II in eel did not affect catecholamine release. α -Adrenoceptor blockade (prazosin; 1 mg kg-1) reduced the pressor effect of exogenous Ang II (500 pmol kg-1) in both species. In eel, intravenous injection of the smooth muscle relaxant papaverine (10 mg kg-1) elicited a rapid decrease in dorsal aortic pressure (PDA; 58 %) followed by a gradual recovery back to the baseline value 85 min after the treatment. In trout, papaverine elicited a similar decrease in blood pressure (62 %); however, PDA recovered fully 20 min after treatment. Blockade of either α -adrenoceptors with prazosin or adrenergic nerves with bretylium (10 mg kg-1) prior to papaverine treatment did not alter PDA recovery in eel. In trout, α -adrenoceptor and adrenergic nerve blockade prior to the papaverine treatment prevented and attenuated PDA recovery, respectively. In both species, papaverine treatment elicited significant increases in plasma catecholamine and Ang II concentrations. However, the increases in plasma catecholamine concentrations were markedly greater in trout than in eel. Similarly, the papaverine-elicited increase in plasma Ang II levels occurred earlier and was greater in trout than in eel. Thus, while Ang II stimulates humoral catecholamine release in trout, there is no evidence for a similar interaction in eel. Moreover, during hypotensive stress, although the renin-angiotensin system is recruited in both species, an essential involvement of adrenergic nerves and humoral catecholamines in the restoration of blood pressure is only apparent in trout.

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