scholarly journals Salt sensitivity of blood pressure in NKCC1-deficient mice

2008 ◽  
Vol 295 (4) ◽  
pp. F1230-F1238 ◽  
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.

Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice

2007 ◽  
Vol 292 (1) ◽  
pp. F415-F422 ◽  
Author(s):  
Soo Mi Kim ◽  
Limeng Chen ◽  
Diane Mizel ◽  
Yuning G. Huang ◽  
Josie P. Briggs ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Genetic Background ◽  
Intraperitoneal Administration ◽  
Plasma Renin ◽  
Specific Requirement ◽  
Wild Type ◽  
Tail Vein ◽  
Cox 2 ◽  
Deficient Mice

In the current experiments, we determined the response of plasma renin concentration (PRC) to acute intraperitoneal administration of furosemide (40 mg/kg), hydralazine (2 mg/kg), isoproterenol (10 mg/kg), candesartan (50 μg), or quinaprilate (50 μg) in conscious wild-type (WT) and cyclooxygenase (COX)-2−/− mice on three different genetic backgrounds (mixed, C57BL/6, 129J). PRC was measured in plasma obtained by tail vein puncture. Basal PRC was significantly lower in COX-2−/− than WT mice independent of genetic background (51, 10, and 17% of WT in mixed, 129J, and C57BL/6). All five acute interventions caused significant increases of PRC in both COX-2+/+ and −/− mice, but the response was consistently less in COX-2-deficient mice (e.g., ΔPRC in ng ANG I·ml−1·h−1 caused by furosemide, isoproterenol, hydralazine, quinaprilate, or candesartan 4,699 ± 544, 3,534 ± 957, 2,522 ± 369, 9,453 ± 1,705, 66,455 ± 21,938 in 129J WT, and 201 ± 78, 869 ± 275, 140 ± 71, 902 ± 304, 2,660 ± 954 in 129J COX-2−/−). A low-NaCl diet and enalapril for 1 wk caused a 14-fold elevation of PRC in COX-2−/− mice and was associated with a greatly increased PRC response to acute furosemide (ΔPRC 201 ± 78 before and 15,984 ± 2,397 after low Na/enalapril). As measured by radiotelemetry, blood pressure and heart rate responses to furosemide, hydralazine, isoproterenol, candesartan, or quinaprilate were not different between COX-2 genotypes. In conclusion, chronic absence of COX-2 reduces renin expression, release, and PRC and is associated with a reduced ability to alter PRC during acute stimulation regardless of the nature of the stimulus. COX-2 activity does not appear to be a mandatory and specific requirement for furosemide-stimulated renin secretion.

Adenosine as a mediator of macula densa-dependent inhibition of renin secretion

2006 ◽  
Vol 290 (5) ◽  
pp. F1016-F1023 ◽  
Author(s):  
Soo Mi Kim ◽  
Diane Mizel ◽  
Yuning G. Huang ◽  
Josie P. Briggs ◽  
Jurgen Schnermann
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Renin ◽  
Macula Densa ◽  
Renin Secretion ◽  
Nacl Transport ◽  
Dependent Inhibition ◽  
Deficient Mice ◽  
Stimulation Of

Adenosine acting through A1 adenosine receptors (A1AR) has been shown previously to be required for the vasoconstriction elicited by high luminal NaCl concentrations at the macula densa (MD). The present experiments were performed to investigate a possible role of A1AR in MD control of renin secretion in conscious wild-type (WT) and A1AR-deficient mice. The intravenous injection of NaCl (5% body wt) reduced plasma renin concentration (PRC; ng ANG I·ml−1·h−1) from 1,479 ± 129 to 711 ± 77 ( P < 0.0001; n = 18) in WT mice but did not significantly change PRC in A1AR−/− mice (1,352 ± 168 during control vs. 1,744 ± 294 following NaCl; P = 0.19; n = 17). NaCl injections also caused a significant reduction in PRC in β1/β2-adrenergic receptor−/− mice (298 ± 47 vs. 183 ± 42; P = 0.03; n = 6). Injections of isotonic NaHCO3 (5% body wt) elicited significant increases in PRC in both WT and A1AR−/− mice. NaCl as well as NaHCO3 injections were accompanied by transient increases in blood pressure, heart rate, and activity that were similar in WT and A1AR−/− mice. The increase in PRC caused by an intraperitoneal injection of furosemide (40 mg/kg) was comparable in WT and A1AR−/− mice, and it was accompanied by similar transient increases in blood pressure, heart rate, and activity. Similarly, the stimulation of PRC caused by hydralazine was the same in WT and A1AR−/− mice. We conclude that the inhibition of renin secretion in response to an increase in NaCl at the MD requires A1AR and therefore appears to be adenosine dependent, whereas the stimulation of renin secretion during reductions in MD NaCl transport or arterial pressure does not require functional A1AR.

Plasma renin activity, angiotensin II, and aldosterone during intense heat stress

1976 ◽  
Vol 41 (3) ◽  
pp. 323-327 ◽  
Author(s):  
K. J. Kosunen ◽  
A. J. Pakarinen ◽  
K. Kuoppasalmi ◽  
H. Adlercreutz
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Heat Stress ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Renin Activity ◽  
Arterial Blood ◽  
Main Components ◽  
Intense Heat

Plasma renin activity (PRA), angiotensin II, and aldosterone levels, arterial blood pressure, and heart rate of six male students were investigated during and after heat stress in a sauna bath. Increased PRA, angiotensin II, and aldosterone levels were found both during and after sauna. The greatest mean increases in PRA (94.9 +/- 10.4% SE, P less than 0.005) and angiotensin II (196 +/- 54.7% SE, P less than 0.02) were observed at the end of the heat stress (at 20 min), and that in plasma aldosterone (505 +/- 209% SE, P less than 0.02) 30 min after the sauna. The heart rate roughly doubled during the heat stress and there was a transient increase followed by a decrease in systolic blood pressure and a decrease in diastolic blood pressure. This study demonstrates that intense heat stress can cause remarkable changes in the three main components of the renin-angiotensin-aldosterone system.

Hypoxia attenuates the renin response to hemorrhage

1992 ◽  
Vol 263 (3) ◽  
pp. R664-R669
Author(s):  
M. R. Eichinger ◽  
J. R. Claybaugh
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Loss ◽  
Atrial Natriuretic Factor ◽  
Blood Pressure Reduction ◽  
Plasma Renin ◽  
Experimental Period ◽  
Pressure Reduction ◽  
Arterial Blood ◽  
Inspired Oxygen

We studied hypoxia and hypotensive hemorrhage in conscious female goats. After control, goats continued an experimental period in normoxia or hypoxia [fractional inspired oxygen concentration (FIO2) = 0.10] for 120 min. After 60 min in the experimental period, a hemorrhage (0.5 ml.kg-1.min-1 for 30 min) was initiated (normoxic hemorrhage, NH; hypoxic hemorrhage, HH). Heart rate (HR) increased 51 +/- 18 beats/min with NH after 30 min of hemorrhage. HR increased 40 +/- 10 beats/min after hypoxic gas introduction, with no further increase during HH. Mean arterial blood pressure (MABP) was reduced 23 +/- 7 mmHg 30 min after completion of blood loss with normoxia but was reduced 23 +/- 7 mmHg at 20 min of HH. Arginine vasopressin (AVP) was increased to 2.60 +/- 2.08 and 160.40 +/- 49.74 microU/ml after 10 and 20 min of HH, respectively, and was only increased after 30 min (87.33 +/- 67.18 microU/ml) of NH. Unexpectedly, plasma renin activity (PRA) increased in parallel in both groups and was doubled at 30 min of hemorrhage. Atrial natriuretic factor was reduced to 8.8 +/- 1.6 pg/ml by 10 min of NH and to 11.4 +/- 3.3 pg/ml at 30 min of HH. Thus hypoxia leads to an earlier development of hypotension and increase in AVP with blood loss but may attenuate the PRA response to blood pressure reduction.

Increased circulating plasma catecholamines and plasma renin activity in dogs after chemical sympathectomy with 6-hydroxydopamine

1977 ◽  
Vol 55 (3) ◽  
pp. 724-733 ◽  
Author(s):  
Gérald A. Porlier ◽  
Réginald A. Nadeau ◽  
Jacques de Champlain ◽  
Daniel G. Bichet
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Renin Activity ◽  
Mean Arterial Blood Pressure ◽  
Plasma Catecholamines ◽  
Plasma Renin ◽  
Renin Activity ◽  
Chemical Sympathectomy ◽  
Arterial Blood ◽  
6 Hydroxydopamine

Circulating plasma catecholamines, plasma renin activity, and other variables were measured in unanesthetized dogs before and after chemical sympathectomy with 6-hydroxydopamine (6-OHDA, 50 mg/kg). Chemical sympathectomy resulted in an immediate fall in mean arterial blood pressure and a delayed reduction in heart rate. Significant increases in plasma glucose and lactate concentrations, circulating plasma catecholamines, and plasma renin activity were found 24 h after 6-OHDA treatment. Circulating catecholamine levels decreased rapidly as time elapsed after sympathectomy and were half the initial values after 2 weeks. Plasma renin activity remained elevated during the 1st week after 6-OHDA treatment and returned to control levels during the 2nd week. Significant correlations were found between circulating catecholamines and heart rate mean arterial pressure, and plasma glucose and lactate concentrations. A significant correlation was also found between plasma renin activity and the mean arterial blood pressure. These results confirm that the adrenal medulla increases its catecholamine secretion rate into the circulation to compensate for the loss of adrenergic innervation after 6-OHDA treatment. They also indicate that the rennin–angiotensin system represents another important compensatory mechanism for circulatory homeostasis in sympathec-tomized animals.

scholarly journals Natriuretic peptides buffer renin-dependent hypertension

2014 ◽  
Vol 306 (12) ◽  
pp. F1489-F1498 ◽  
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.

Intravenous acid infusion stimulates ACTH secretion in sheep

1991 ◽  
Vol 260 (1) ◽  
pp. E154-E161 ◽  
Author(s):  
C. E. Wood ◽  
A. Isa
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Lactic Acid ◽  
Plasma Renin Activity ◽  
Vena Cava ◽  
Plasma Renin ◽  
Renin Activity ◽  
Acth Secretion ◽  
Reflex Responses ◽  
Arterial Blood

Both respiratory and metabolic acidemia stimulate the secretion of adrenocorticotropic hormone (ACTH), vasopressin, and renin. The present study was designed to test the blood pressure, heart rate, and endocrine responses of conscious sheep to low-rate infusions of H+. We infused HCl and lactic acid at a rate of 500 mueq/min into the inferior vena cava of seven chronically catheterized adult sheep. Control experiments in six sheep consisted of infusion of HCl at a rate of 100 mueq/min. Only the 500 mueq/min infusion of HCl stimulated reflex responses. This infusion increased mean arterial blood pressure and plasma ACTH concentration but transiently decreased blood pH only after the onset of the reflex responses. Heart rate appeared to increase initially but then decreased. Overall, the apparent changes in heart rate were not statistically significant. None of the infusions significantly altered plasma renin activity or vasopressin concentration. We speculate that heart rate, plasma renin activity, and vasopressin may have been partially inhibited by the increase in blood pressure. However, the lack of effect of lactic acid suggests that the HCl stimulated reflex ACTH and blood pressure responses via a mechanism not related to the concentration of the acid in the infusate or to the total amount of acid infused. It is possible that HCl, but not lactic acid, stimulated release of a humoral agent that stimulated ACTH secretion directly or reflexly. The results do not appear consistent with the stimulation of a venous chemoreceptor sensitive to H+.

Reflex inhibition of plasma renin activity by increased left ventricular pressure in conscious dogs

1989 ◽  
Vol 256 (6) ◽  
pp. R1299-R1307
Author(s):  
A. J. Gorman ◽  
J. S. Chen
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Renin Activity ◽  
Arterial Blood Pressure ◽  
Left Atrial ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Renin Activity ◽  
Conscious Dogs ◽  
Arterial Blood

The purpose of the present study was to determine the effects of left ventricular (LV) outflow obstruction on plasma renin activity (PRA) and the contribution from afferent receptors located in the LV myocardium. In chronically instrumented, conscious dogs (n = 12), changes in PRA during a 15- to 20-mmHg decrease in arterial blood pressure were assessed during 1) intravenous infusions of nitroprusside (NP) alone and 2) infusions of NP while peak systolic LV pressure was elevated by acute ascending aortic occlusion (AAO + NP). Infusions of NP alone elicited significant increases in heart rate (24.9 +/- 5.1 beats/min; P less than 0.01) and in PRA [3.31 +/- 0.53 ng angiotensin I (ANG I).ml-1.h-1; P less than 0.01]. These were accompanied by decreases in both LV pressure (-13.8 +/- 3.6 mmHg; P less than 0.05) and left atrial pressure (-3.0 +/- 0.7 mmHg; P less than 0.05). During AAO + NP, LV pressure was elevated to an absolute level of 169.2 +/- 4.6 mmHg (+53.3 +/- 4.2 mmHg; P less than 0.001), whereas left atrial pressure was not changed. Both the hypotension-induced rise in PRA and tachycardia were significantly inhibited during AAO + NP (+0.59 +/- 0.29 ng ANG I.ml-1.h-1 and +6.3 +/- 4.6 beats/min, respectively; NS). The topical application of a local anesthetic in the region of the main coronary artery, sufficient to block the heart rate and arterial blood pressure responses to selective LV receptor stimulation by intracoronary veratridine (0.1-0.4 microgram/kg), resulted in significant increases in PRA and heart rate during AAO + NP.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of renin in mice with Cre recombinase-mediated deletion of G protein Gsα in juxtaglomerular cells

2007 ◽  
Vol 292 (1) ◽  
pp. F27-F37 ◽  
Author(s):  
Limeng Chen ◽  
Soo Mi Kim ◽  
Mona Oppermann ◽  
Robert Faulhaber-Walter ◽  
Yuning Huang ◽  
...  
Keyword(s):  
Renal Medulla ◽  
Plasma Renin ◽  
Cre Recombinase ◽  
Wild Type ◽  
Complete Excision ◽  
Arterial Blood ◽  
Renin Synthesis ◽  
Gnas Gene ◽  
Exon 1 ◽  
Deficient Mice

By crossing mice with expression of Cre recombinase under control of the endogenous renin promoter (Sequeira Lopez ML, Pentz ES, Nomasa T, Smithies O, Gomez RA. Dev Cell 6: 719–728, 2004) with mice in which exon 1 of the Gnas gene was flanked by loxP sites (Chen M, Gavrilova O, Liu J, Xie T, Deng C, Nguyen AT, Nackers LM, Lorenzo J, Shen L, Weinstein LS. Proc Natl Acad Sci USA), we generated animals with preferential and nearly complete excision of Gsα in juxtaglomerular granular (JG) cells. Compared with wild-type animals, mice with conditional Gsα deficiency had markedly reduced basal levels of renin expression and very low plasma renin concentrations. Furthermore, the acute release responses to furosemide, hydralazine, and isoproterenol were virtually abolished. Consistent with a state of primary renin depletion, Gsα-deficient mice had reduced arterial blood pressure, reduced levels of aldosterone, and a low glomerular filtration rate. Renin content and renin secretion of JG cells in primary culture were drastically reduced, and the stimulatory response to the addition of PGE2 or isoproterenol was eliminated. Unexpectedly, Gsα recombination was also observed in the renal medulla, and this was associated with a vasopressin-resistant concentrating defect. Our study shows that Cre recombinase under control of the renin promoter can be used for the excision of floxed targets from JG cells. We conclude that Gsα-mediated signal transduction is essential and nonredundant in the control of renin synthesis and release.

Involvement of Prostaglandins in the Actions of Captopril

1982 ◽  
Vol 63 (s8) ◽  
pp. 265s-267s ◽  
Author(s):  
H. Witzgall ◽  
B. Scherer ◽  
P. C. Weber
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Renin Activity ◽  
Urine Volume ◽  
Plasma Renin ◽  
Potassium Excretion ◽  
Arterial Blood ◽  
Pg E2 ◽  
Excretion Rates ◽  
Sodium And Potassium

1. Haemodynamic and hormonal actions of 100 mg of captopril (SQ 14 225) orally were tested in 12 healthy volunteers with and without indomethacin pretreatment. 2. Without indomethacin, mean arterial blood pressure was reduced at 30 and 60 min after captopril (P < 0.02). Heart rate did not change. Plasma renin activity (PRA) increased (P < 0.002), and plasma and urinary aldosterone as well as plasma 18-hydroxycorticosterone (18- OH-B) decreased after captopril (P < 0.02). Prostaglandin (PG) E2, kallikrein, urine volume, sodium and potassium excretion rates remained constant after captopril. 3. Under indomethacin pretreatment, blood pressure was reduced to a smaller degree at 30 and 60 min after captopril (P < 0.05). Heart rate was constantly lower than without indomethacin (P < 0.05). Indomethacin decreased basal PGE2 and kallikrein excretion (P < 0.02) and reduced basal PRA as well as the increase of PRA after captopril (P < 0.05). Basal mineralocorticoid levels were significantly lower than without indomethacin. Aldosterone did not decrease further after captopril, and 18-OH-B fell only slightly. 4. The results suggest that prostaglandins may be involved in the haemodynamic and hormonal actions of captopril.

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