Local inhibition of nitric oxide temporarily stimulates aldosterone secretion in conscious sheep in vivo

2001 ◽  
Vol 280 (4) ◽  
pp. E584-E590 ◽  
Author(s):  
Renato Salemi ◽  
John G. McDougall ◽  
Kenneth J. Hardy ◽  
E. Marelyn Wintour
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Secretion Rate ◽  
Aldosterone Secretion ◽  
Local Inhibition ◽  
Negative Effect ◽  
Endogenous Nitric Oxide ◽  
Conscious Sheep ◽  
Time Point

The effect of localized blockage of endogenous nitric oxide (NO) on basal aldosterone secretion was studied in conscious sheep with autotransplanted adrenal glands. We have shown that infusion of the NO synthase (NOS) inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 130 μg/l blood flow) significantly stimulated basal aldosterone secretion rate (ASR). This stimulatory effect was seen up to 4 h of infusion. Beyond this time point, however, the elevated ASR level was not sustained, and it was seen to drop markedly to lower than control values at 5 h. l-NAME had no effect on cortisol secretion rate (FSR) during the first 4 h of infusion, but a significant reduction in FSR was seen by the 8-h time point. Adrenal blood flow was consistently decreased in association with long l-NAME infusion. Additionally, l-NAME was shown to have no effect on aldosterone secretion when infused systemically. We conclude that the relationship between NO and aldosterone secretion is an inhibitory one, in which NO seems to have a negative effect on basal aldosterone secretion.

Adrenocortical metabolism of angiotensin in sheep with adrenal transplants.

1978 ◽  
Vol 235 (5) ◽  
pp. E525
Author(s):  
S Lun ◽  
E A Espiner ◽  
D S Hart
Keyword(s):  
Blood Flow ◽  
Adrenal Gland ◽  
Secretion Rate ◽  
Aldosterone Secretion ◽  
Adrenal Tissue ◽  
Rate Analysis ◽  
Venous Plasma

Conscious trained sheep with adrenal gland autotransplants in cervical skin loops were used to study adrenocortical metabolism and clearance of angiotensin (AII) administered by constant systemic infusion. For comparative purposes similar experiments were undertaken in five control sheep with skin loops but no cervical adrenal tissue. During AII infusions (0.33 microgram/min for 30 min), loop venous-arterial AII ratios (0.42--0.62 were similar in both groups of sheep. Measured AII clearances across the skin loop in sheep with and without adrenal transplants were 400--600 and 100--150 pg/min, respectively, which correlated with blood flow (r = 0.79), but showed no relation to aldosterone secretion rate. Analysis of AII immunoreactive fragments showed similar proportions of octa-, hepta-, and hexapeptide fractions (64, 26, and 5%, respectively) in adrenal arterial, adrenal venous, and systemic venous plasma. These studies do not support selective heptapeptide uptake or metabolism by adrenal tissue in vivo and indicate that specific adrenal binding of AII is likely to be less than 400 pg/min at arterial AII concentrations approximating 120 pg/ml.

Disruption of TRPV1-mediated coupling of coronary blood flow to cardiac metabolism in diabetic mice: role of nitric oxide and BK channels

2012 ◽  
Vol 303 (2) ◽  
pp. H216-H223 ◽  
Author(s):  
Giacinta Guarini ◽  
Vahagn A. Ohanyan ◽  
John G. Kmetz ◽  
Daniel J. DelloStritto ◽  
Roslin J. Thoppil ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Cardiac Metabolism ◽  
Bk Channels ◽  
Bk Channel ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Channel Dependent

We have previously shown transient receptor potential vanilloid subtype 1 (TRPV1) channel-dependent coronary function is compromised in pigs with metabolic syndrome (MetS). However, the mechanisms through which TRPV1 channels couple coronary blood flow to metabolism are not fully understood. We employed mice lacking TRPV1 [TRPV1(−/−)], db/db diabetic, and control C57BKS/J mice to determine the extent to which TRPV1 channels modulate coronary function and contribute to vascular dysfunction in diabetic cardiomyopathy. Animals were subjected to in vivo infusion of the TRPV1 agonist capsaicin to examine the hemodynamic actions of TRPV1 activation. Capsaicin (1–100 μg·kg−1·min−1) dose dependently increased coronary blood flow in control mice, which was inhibited by the TRPV1 antagonist capsazepine or the nitric oxide synthase (NOS) inhibitor N-nitro-l-arginine methyl ester (l-NAME). In addition, the capsaicin-mediated increase in blood flow was attenuated in db/db mice. TRPV1(−/−) mice exhibited no changes in coronary blood flow in response to capsaicin. Vasoreactivity studies in isolated pressurized mouse coronary microvessels revealed a capsaicin-dependent relaxation that was inhibited by the TRPV1 inhibitor SB366791 l-NAME and to the large conductance calcium-sensitive potassium channel (BK) inhibitors iberiotoxin and Penetrim A. Similar to in vivo responses, capsaicin-mediated relaxation was impaired in db/db mice compared with controls. Changes in pH (pH 7.4–6.0) relaxed coronary vessels contracted to the thromboxane mimetic U46619 in all three groups of mice; however, pH-mediated relaxation was blunted in vessels obtained from TRPV1(−/−) and db/db mice compared with controls. Western blot analysis revealed decreased myocardial TRPV1 protein expression in db/db mice compared with controls. Our data reveal TRPV1 channels mediate coupling of myocardial blood flow to cardiac metabolism via a nitric oxide-dependent, BK channel-dependent pathway that is corrupted in diabetes.

Dilator actions of arginine in human peripheral vasculature

1991 ◽  
Vol 81 (5) ◽  
pp. 695-700 ◽  
Author(s):  
Alison Calver ◽  
Joe Collier ◽  
Patrick Vallance
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Forearm Blood Flow ◽  
Hypotensive Effect ◽  
Linear Displacement ◽  
High Dose ◽  
Free Base ◽  
Peripheral Vasculature ◽  
Arginine Hydrochloride

1. l-Arginine is the physiological precursor for the formation of endothelium-derived nitric oxide. The synthesis of nitric oxide is stereospecific: d-arginine is not a substrate for nitric oxide synthase. It is possible that the provision of excess l-arginine substrate might increase the vascular synthesis of nitric oxide. We have examined this possibility by studying the effects of local infusion of l-and d-arginine in the forearm resistance bed and the superficial dorsal hand veins of healthy subjects. 2. Drugs were either infused locally into a vein on the back of the hand and then the vein diameter was measured using a linear displacement technique, or into the brachial artery and then the forearm blood flow was measured by venous occlusion plethysmography. 3. In the superficial hand veins, l- and d-arginine free base and l- and d-arginine hydrochloride (all four preparations at a dose of 5 μmol/min) all caused a significant increase in venous diameter. The responses of the l-and d-enantiomers did not differ significantly from one another. 4. In the forearm resistance bed, l- and d-arginine free base and l-arginine hydrochloride were without effect at doses of 10 and 40 μmol/min. However, at doses of 160 μmol/min all three preparations of arginine caused a significant increase in forearm blood flow compared with control values. The responses to the three preparations of arginine did not differ significantly from one another. 5. These results show that arginine in high dose is a vasodilator in both human resistance vessels and superficial veins in vivo. The response to arginine was not stereospecific: both the l- and d-enantiomers had the same effect. The dilator effect of high-dose arginine showed neither arterio-nor veno-selectivity. 6. This suggests that the hypotensive effect of systemic infusions of l-arginine in man is mediated by peripheral vasodilatation. It is not possible to ascribe the actions of arginine supplementation in this study to activation of the l-arginine/nitric oxide pathway through the provision of excess substrate.

S-nitroso-albumin carries a thiol-labile pool of nitric oxide, which causes venodilation in the rat

2005 ◽  
Vol 289 (2) ◽  
pp. H916-H923 ◽  
Author(s):  
Nelson N. Orie ◽  
Patrick Vallance ◽  
Dean P. Jones ◽  
Kevin P. Moore
Keyword(s):  
Nitric Oxide ◽  
Molecular Weight ◽  
Blood Flow ◽  
Vascular Function ◽  
Low Molecular Weight ◽  
Aortic Blood Flow ◽  
Hemodynamic Effects ◽  
Rapid Decomposition ◽  
Aortic Blood

It is now established that S-nitroso-albumin (SNO-albumin) circulates at low nanomolar concentrations under physiological conditions, but concentrations may increase to micromolar levels during disease states (e.g., cirrhosis or endotoxemia). This study tested the hypothesis that high concentrations of SNO-albumin observed in some diseases modulate vascular function and that it acts as a stable reservoir of nitric oxide (NO), releasing this molecule when the concentrations of low-molecular-weight thiols are increased. SNO-albumin was infused into rats to increase the plasma concentration from <50 nmol/l to ∼4 μmol/l. This caused a 29 ± 6% drop in blood pressure, 20 ± 4% decrease in aortic blood flow, and a 25 ± 14% reduction of renal blood flow within 10 min. These observations were in striking contrast to those of an infused arterial vasodilator (hydralazine), which increased aortic blood flow, and suggested that SNO-albumin acts primarily as a venodilator in vivo. This was confirmed by the observations that glyceryl trinitrate (a venodilator) led to similar hemodynamic changes and that the hemodynamic effects of SNO-albumin are reversed by infusion of colloid. Infusion of N-acetylcysteine into animals with artificially elevated plasma SNO-albumin concentrations led to the rapid decomposition of SNO-albumin in vivo and reproduced the hemodynamic effects of SNO-albumin infusion. These data demonstrate that SNO-albumin acts primarily as a venodilator in vivo and represents a stable reservoir of NO that can release NO when the concentrations of low-molecular-weight thiols are elevated.

Abstract 3628: Neuronal Nitric Oxide Synthase (nNOS) Regulates Basal Flow in the Human Coronary Circulation I n Vivo

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mike Seddon ◽  
Phil Chowienczyk ◽  
Narbeh Melikian ◽  
Rafal Dworakowski ◽  
Barbara Casadei ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Coronary Flow ◽  
Vascular Tone ◽  
Coronary Circulation ◽  
Physiological Regulation ◽  
Intracoronary Doppler ◽  
Basal Flow

Endothelial NO synthase (eNOS) is thought to be the major source of nitric oxide (NO) involved in the local regulation of human vascular tone. However, in studies using a selective neuronal NOS (nNOS) inhibitor S-methyl-L-thiocitrulline (SMTC), we recently reported that basal human forearm blood flow is regulated by nNOS. SMTC had no effect on acetylcholine-induced vasodilatation which however was inhibited by the non-selective NOS inhibitor N G monomethyl-L-arginine (L-NMMA). This study investigated the effects of nNOS in the human coronary circulation in vivo . We studied patients undergoing diagnostic cardiac catheterisation who had angiographically normal coronary arteries. Coronary flow velocity was measured by an intracoronary Doppler wire and epicardial artery diameter by QCA. We compared the effects of intracoronary SMTC or L-NMMA infusion on basal flow and the responses to substance P and isosorbide dinitrate (endothelium-dependent and -independent dilators, respectively). L-NMMA (25 μmol/min) reduced basal coronary flow by 22.3±5.3% and inhibited dilation to substance P (20 pmol/min) by 57±5.7% (n=8; both P<0.01). SMTC (0.625 μmol/min) also reduced basal flow (−34.8±6.3%; n=8; P<0.01), but had no effect on the response to substance P (inhibited by −2±14%; P=NS). The effects of SMTC were abolished by L-arginine (240μmol/ min; n=3). Both L-NMMA and SMTC reduced epicardial artery diameter (−2.5±0.6% and −2.8±0.9% respectively; P<0.05) but only L-NMMA reduced dilatation to substance P (5.6±1.3% before versus 3.0±0.8% after L-NMMA; P<0.05). These data indicate that local nNOS-derived NO regulates basal coronary blood flow in humans in vivo , whereas substance P-stimulated vasodilatation is eNOS-mediated. Our results indicate that nNOS and eNOS have distinct local roles in the physiological regulation of human coronary vascular tone in vivo .

scholarly journals Nitric oxide production duringVibrio choleraeinfection

1997 ◽  
Vol 273 (5) ◽  
pp. G1160-G1167 ◽  
Author(s):  
Edward N. Janoff ◽  
Hiroshi Hayakawa ◽  
David N. Taylor ◽  
Claudine E. Fasching ◽  
Julie R. Kenner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Epithelial Cells ◽  
Regional Blood Flow ◽  
Fluid Secretion ◽  
The United States ◽  
No Production ◽  
Loop Model ◽  
Ileal Loop

Vibrio cholerae induces massive intestinal fluid secretion that continues for the life of the stimulated epithelial cells. Enhanced regional blood flow and peristalsis are required to adapt to this obligatory intestinal secretory challenge. Nitric oxide (NO) is a multifunctional molecule that modulates blood flow and peristalsis and possesses both cytotoxic and antibacterial activity. We demonstrate that, compared with those in asymptomatic control subjects, levels of stable NO metabolites ([Formula: see text]/[Formula: see text]) are significantly increased in sera from acutely ill Peruvian patients with natural cholera infection as well as from symptomatic volunteers from the United States infected experimentally with V. cholerae. In a rabbit ileal loop model in vivo, cholera toxin (CT) elicited fluid secretion and dose-dependent increases in levels of[Formula: see text]/[Formula: see text]in the fluid ( P < 0.01). In contrast, lipopolysaccharide (LPS) elicited no such effects when applied to the intact mucosa. NO synthase (NOS) catalytic activity also increased in toxin-exposed tissues ( P< 0.05), predominantly in epithelial cells. The CT-induced NOS activity was Ca2+dependent and was not suppressed by dexamethasone. In conclusion, symptomatic V. cholerae infection induces NO production in humans. In the related animal model, CT, but not LPS, stimulated significant production of NO in association with increases in local Ca2+-dependent NOS activity in the tissues.

Glucocorticoid-induced renal vasodilatation is mediated by a direct renal action involving nitric oxide

1997 ◽  
Vol 273 (6) ◽  
pp. R1972-R1979 ◽  
Author(s):  
R. De Matteo ◽  
C. N. May
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Plasma Cortisol ◽  
Filtration Rate ◽  
Systemic Effects ◽  
Renal Vasculature ◽  
Relaxing Factor ◽  
Renal Action ◽  
Endothelium Derived Relaxing Factor ◽  
Conscious Sheep

Glucocorticoids increase renal blood flow (RBF) and glomerular filtration rate, but the mechanisms are unclear. We investigated whether the cortisol-induced increment in RBF is a direct renal action or secondary to its systemic effects and whether nitric oxide (NO) plays a role in this response. In conscious sheep, cortisol infused intravenously (5.0 mg/h) or into the renal artery (1.3 mg/h) for 5 h increased RBF by 66 ± 8 and 53 ± 11 ml/min, respectively. Plasma glucose was increased by intravenous cortisol (0.4 ± 0.1 mmol/l) but not by intrarenal cortisol. Renal vein plasma cortisol levels were similar at the end of each infusion (193 ± 31 intravenously; 151 ± 25 nmol/l intrarenal), but systemic levels were different (277 ± 31 intravenous; 69 ± 10 nmol/l intrarenal). Inhibition of NO synthesis by N ω-nitro-l-arginine infused intravenously (10 mg/kg followed by 5 mg ⋅ kg−1 ⋅ h−1) or intrarenally (2 mg ⋅ kg−1 ⋅ h−1) significantly reduced the cortisol-induced renal vasodilatation. In contrast, constriction of the renal vasculature with intrarenal angiotensin (0.3 μg/h) did not prevent the cortisol-induced renal vasodilatation. These findings demonstrate that cortisol acts directly on the kidney to cause renal vasodilatation and to increase RBF and suggest that this response involves the endothelium-derived relaxing factor NO.

In vivo assessment of microvascular nitric oxide production and its relation with blood flow

2001 ◽  
Vol 280 (3) ◽  
pp. H1222-H1231 ◽  
Author(s):  
X. F. Figueroa ◽  
A. D. Martínez ◽  
D. R. González ◽  
P. I. Jara ◽  
S. Ayala ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Plasma Flow ◽  
Subcellular Fractionation ◽  
No Synthase ◽  
Cheek Pouch ◽  
No Production ◽  
Hamster Cheek Pouch ◽  
Membrane Bound

To assess the hypothesis that microvascular nitric oxide (NO) is critical to maintain blood flow and solute exchange, we quantified NO production in the hamster cheek pouch in vivo, correlating it with vascular dynamics. Hamsters (100–120 g) were anesthetized and prepared for measurement of microvessel diameters by intravital microscopy, of plasma flow by isotopic sodium clearance, and of NO production by chemiluminescence. Analysis of endothelial NO synthase (eNOS) location by immunocytochemistry and subcellular fractionation revealed that eNOS was present in arterioles and venules and was 67 ± 7% membrane bound. Basal NO release was 60.1 ± 5.1 pM/min ( n = 35), and plasma flow was 2.95 ± 0.27 μl/min ( n = 29). Local NO synthase inhibition with 30 μM N ω-nitro-l-arginine reduced NO production to 8.6 ± 2.6 pmol/min (−83 ± 5%, n = 9) and plasma flow to 1.95 ± 0.15 μl/min (−28 ± 12%, n = 17) within 30–45 min, in parallel with constriction of arterioles (9–14%) and venules (19–25%). The effects of N ω-nitro-l-arginine (10–30 μM) were proportional to basal microvascular conductance ( r = 0.7, P < 0.05) and fully prevented by 1 mM l-arginine. We conclude that in this tissue, NO production contributes to 35–50% of resting microvascular conductance and plasma-tissue exchange.

IN VITRO AND IN VIVO EFFECT OF GROWTH HORMONE ON ALDOSTERONE SECRETION

1960 ◽  
Vol 38 (1) ◽  
pp. 1069-1075
Author(s):  
O. J. Lucis ◽  
E. H. Venning
Keyword(s):  
Growth Hormone ◽  
Adrenal Gland ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Secretion Rate ◽  
Aldosterone Secretion ◽  
Hypophysectomized Rats

Porcine, monkey, and human growth hormone have no effect on the in vitro secretion of aldosterone by the rat adrenal gland. When monkey growth hormone is injected into hypophysectomized rats, the adrenals of these animals secrete, under in vitro conditions, increased amounts of aldosterone with no change in the secretion rate of corticosterone. The plasma of these rats contains a substance which appears to stimulate the secretion of aldosterone in the adrenals of normal rats.

Sign in / Sign up

Export Citation Format

Share Document