scholarly journals Nitric oxide may be required to prevent hypertension at the onset of diabetes

2000 ◽  
Vol 279 (4) ◽  
pp. E762-E768 ◽  
Author(s):  
Sharyn M. Fitzgerald ◽  
Michael W. Brands
Keyword(s):  
Nitric Oxide ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Pressure Control ◽  
Progressive Increase ◽  
Onset Of Diabetes ◽  
Regulation Of Vascular Tone

Nitric oxide (NO) plays an important role in the regulation of vascular tone, and evidence suggests that endothelial-dependent relaxation, possibly mediated via NO, is impaired in diabetes. However, the role of the endothelium in arterial pressure control early in diabetes, before dysfunction develops, is not known. This was evaluated in the present study by comparing the responses to induction of diabetes in vehicle-treated rats (D, n = 7) vs. rats chronically treated with N G-nitro-l-arginine methyl ester (l-NAME; D+L, n = 8). A nondiabetic group also was treated with l-NAME (L, n = 7) to control for l-NAME effects over time, independent of diabetes. After baseline measurements, rats were given either vehicle or l-NAME (10 μg · kg−1 · min−1 iv) infusion throughout the experiment. Six days later, streptozotocin (60 mg/kg iv) was administered, followed by a 3-wk diabetic study period. Induction of diabetes in the D+L rats caused a marked and progressive increase in mean arterial pressure throughout the diabetic period, averaging ∼70 mmHg greater than in the D rats and ∼20 mmHg greater than in the L rats. Glomerular filtration rate and renal plasma flow tended to increase during diabetes, but this trend was reversed in the D+L rats. In addition, plasma renin activity increased in the D and D+L rats during week 1 of diabetes but then returned to control in the D rats, while continuing to increase in the D+L rats. These results suggest that, in the early stages of diabetes, NO synthesis is important to prevent hypertension from developing, possibly through actions to maintain glomerular filtration and suppress renin secretion.

scholarly journals Nitric oxide: a potential mediator of amino acid-induced renal hyperemia and hyperfiltration.

1991 ◽  
Vol 1 (12) ◽  
pp. 1271-1277
Author(s):  
A J King ◽  
J L Troy ◽  
S Anderson ◽  
J R Neuringer ◽  
M Gunning ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glomerular Filtration Rate ◽  
Amino Acid ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Competitive Inhibitor ◽  
Arterial Blood

The role of nitric oxide in the modulation of systemic and renal hemodynamics was examined by using N omega-monomethyl-L-arginine (L-NMMA, 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused intravenously into anesthetized euvolemic Munich-Wistar rats. After 30 min, L-NMMA resulted in a uniform increase in mean arterial blood pressure (111 +/- 1 to 128 +/- 2 mmHg; P less than 0.05) and a modest reduction in renal plasma flow rate (4.4 +/- 0.2 to 4.2 +/- 0.1 mL/min; P less than 0.05), without change in glomerular filtration rate (1.16 +/- 0.03 to 1.15 +/- 0.03 mL/min); vehicle had no effect on these renal parameters. These rats were then subdivided to receive an intravenous infusion (37 microL/min) of either 10% glycine, 11.4% mixed amino acids, or equiosmolar dextrose. L-NMMA pretreatment markedly attenuated glycine-induced hyperfiltration (10 +/- 6 versus 33 +/- 5%, L-NMMA versus vehicle; P less than 0.05) and obliterated the renal hyperemic response (-7 +/- 6 versus 16 +/- 4%, L-NMMA versus vehicle; P less than 0.05). L-NMMA also caused modest blunting of the mixed amino acid-induced hyperfiltration (18 +/- 4 versus 30 +/- 4%, L-NMMA versus vehicle; P = 0.056) but failed to curtail the renal hyperemia (16 +/- 6 versus 20 +/- 4%). Dextrose had no effect on glomerular filtration rate or renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of salt-sensitive hypertension: role of inducible nitric oxide synthase

2000 ◽  
Vol 279 (6) ◽  
pp. R2297-R2303 ◽  
Author(s):  
Dunyong Y. Tan ◽  
Shumei Meng ◽  
Garrick W. Cason ◽  
R. Davis Manning
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Arterial Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Plasma Renin ◽  
Hormonal Changes ◽  
Oxide Synthase ◽  
Salt Sensitive Hypertension ◽  
Inducible Nitric Oxide

The goal of this study was to determine the role of inducible nitric oxide synthase (iNOS) in the arterial pressure, renal hemodynamic, renal excretory, and hormonal changes that occur in Dahl/Rapp salt-resistant (R) and salt-sensitive (S) rats during changes in Na intake. Thirty-two R and S rats, equipped with indwelling arterial and venous catheters, were subjected to low (0.87 mmol/day) or high (20.6 mmol/day) Na intake, and selective iNOS inhibition was achieved with intravenous aminoguanidine (AG, 12.3 mg · kg−1 · h−1). After 5 days of AG, mean arterial pressure increased to 121 ± 3% control in the R-high Na AG rats compared with 98 ± 1% control ( P < 0.05) in the R-high Na alone rats, and S-high Na rats increased their arterial pressure to 123 ± 3% control compared with 110 ± 2% control ( P < 0.05) in S-high Na alone rats. AG caused no significant changes in renal hemodynamics, urinary Na or H2O excretion, plasma renin activity, or cerebellar Ca-dependent NOS activity. The data suggest that nitric oxide produced by iNOS normally helps to prevent salt-sensitive hypertension in the Dahl R rat and decreases salt sensitivity in the Dahl S rat.

Role of nitric oxide in modulating renal function and arterial pressure during chronic aldosterone excess

1999 ◽  
Vol 276 (1) ◽  
pp. R197-R202 ◽  
Author(s):  
Joey P. Granger ◽  
Salah Kassab ◽  
Jacqueline Novak ◽  
Jane F. Reckelhoff ◽  
Brett Tucker ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Arterial Pressure ◽  
Volume Expansion ◽  
Renal Plasma Flow ◽  
Extracellular Fluid ◽  
Sodium Retention ◽  
Long Term Effects ◽  
Synthesis Inhibitor

Chronic aldosterone (Aldo) excess is associated with transient sodium retention, extracellular fluid volume expansion, renal vasodilation, and hypertension. The purpose of this study was to determine the role of nitric oxide (NO) in mediating the renal vasodilation and the escape from the sodium-retaining actions of Aldo. To achieve this goal, we examined the long-term effects of Aldo (15 μg ⋅ kg−1 ⋅ min−1for 7 days) in conscious, chronically instrumented control dogs ( n = 9) and in dogs ( n = 12) pretreated with the NO synthesis inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 10 μg ⋅ kg−1 ⋅ min−1). In control dogs, Aldo caused a transient sodium retention (126 ± 6 to 56 ± 2 meq/day) followed by a return of sodium excretion to normal levels. Aldo also increased renal plasma flow by 15% (205 ± 13 to 233 ± 16 ml/min), glomerular filtration rate by 20% (72 ± 3 to 87 ± 5 ml/min), and arterial pressure from 90 ± 3 to 102 ± 3 mmHg. Aldo increased urinary nitrate/nitrite excretion by 60% in the control dogs. Although the sodium-retaining (144 ± 7 to 56 ± 7 meq/day) and arterial pressure (122 ± 6 to 136 ± 5 mmHg) responses to Aldo were the same in dogs pretreated withl-NAME compared with control, the renal hemodynamic response was markedly attenuated. The results of this study suggest that NO plays an important role in mediating the renal vasodilation during chronic Aldo excess.

Effect of Narcotic Agents and of Bleeding on Systemic and Renal Haemodynamics in Healthy and CCl4-treated Cirrhotic Rats

1997 ◽  
Vol 93 (6) ◽  
pp. 549-556 ◽  
Author(s):  
G. Van Roey ◽  
P. Lijnen ◽  
R. Verbesselt ◽  
A. Verbruggen ◽  
J. Fevery
Keyword(s):  
Arterial Pressure ◽  
Plasma Volume ◽  
Renal Plasma Flow ◽  
Portal Pressure ◽  
Plasma Renin ◽  
Repeated Measurements ◽  
Peripheral Vasodilatation ◽  
Profound Hypotension ◽  
Awake Rat ◽  
Related Mortality

1. The haemodynamic effects of different narcotic agents have been tested in healthy rats and in rats with cirrhosis. 2. Pentobarbital suppresses the sympathetic nervous system. Susceptibility to ketamine is unpredictable, leading to both insufficient pain relief and narcosis related mortality. The combination diazepam—fluanisone induces profound hypotension. After insertion of catheters, awake, freely moving rats are stable and not distressed. This allows repeated measurements after manipulation. Moreover, procedure-related mortality is low and rats have a better stress response. 3. In the awake animal, arterial pressure is 126 ± 10 for healthy animals, and 111 ± 16 and 102 ± 10 mmHg for cirrhotic animals without and with ascites, respectively (P = 0.018). The respective values for portal pressure are 6.9 ± 1.4, 11.6 ± 2.5 and 16.2 ± 2.9 mmHg (P = 0.0001). After a bleeding, arterial pressure is better preserved than portal pressure in the three groups (P < 0.0001). Plasma volume in cirrhotic rats exceeds that of healthy rats. Plasma renin activity, aldosterone and catecholamines do not differ between the groups studied. In cirrhotic rats with and without ascites, glomerular filtration rate tends to be higher (P = 0.12), renal plasma flow is elevated (P = 0.001) and nitration fraction is lower (P = 0.002) than in healthy rats. 4. In conclusion, haemodynamic experiments in the cirrhotic rat should be performed in the awake rat. Arterial hypotension, impaired filtration fraction, enlarged plasma volume and portal hypertension are present in cirrhosis before the development of ascites. This can as well be explained by splanchnic pooling of blood, as by peripheral vasodilatation. The decrease in portal pressure with preserved arterial pressure after a bleeding protects cirrhotic rats from ongoing variceal bleeding.

Genetic co-segregation of renal haemodynamics and blood pressure in the spontaneously hypertensive rat

1988 ◽  
Vol 74 (1) ◽  
pp. 63-69 ◽  
Author(s):  
S. B. Harrap ◽  
A. E. Doyle
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Spontaneously Hypertensive Rat ◽  
Plasma Renin ◽  
Spontaneously Hypertensive

1. To determine the relevance of renal circulatory abnormalities found in the immature spontaneously hypertensive rat (SHR) to the genetic hypertensive process, glomerular filtration rate and renal blood flow were measured in conscious F2 rats, derived from crossbreeding SHR and normotensive Wistar–Kyoto rats (WKY), at 4, 11 and 16 weeks of age by determining the renal clearances of 51Cr-ethylenediaminetetra-acetate and 125I-hippuran respectively. Plasma renin activity was measured at 11 and 16 weeks of age. 2. Mean arterial pressure, glomerular filtration rate and renal blood flow increased between 4 and 11 weeks of age. Between 11 and 16 weeks the mean glomerular filtration rate and renal blood flow did not alter, although the mean arterial pressure rose significantly. At 11 weeks of age, during the developmental phase of hypertension, a significant negative correlation between mean arterial pressure and both glomerular filtration rate and renal blood flow was noted. However, by 16 weeks when the manifestations of genetic hypertension were more fully expressed, no correlation between mean arterial pressure and renal blood flow or glomerular filtration rate was observed. Plasma renin activity was negatively correlated with both glomerular filtration rate and renal blood flow, but the relationship was stronger at 11 than at 16 weeks of age. 3. These results suggest that the reduction in renal blood flow and glomerular filtration rate, found in immature SHR, is genetically linked to the hypertension and may be of primary pathogenetic importance. It is proposed that the increased renal vascular resistance in these young animals stimulates the rise of systemic arterial pressure which returns renal blood flow and glomerular filtration rate to normal.

scholarly journals Role of endothelial nitric oxide in control of peripheral vascular conductance during muscle metaboreflex activation

2017 ◽  
Vol 313 (1) ◽  
pp. R29-R34
Author(s):  
Danielle Senador ◽  
Jasdeep Kaur ◽  
Alberto Alvarez ◽  
Hanna W. Hanna ◽  
Abhinav C. Krishnan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Output ◽  
Arterial Pressure ◽  
Vascular Conductance ◽  
Muscle Metaboreflex ◽  
Peripheral Vasodilation ◽  
Dependent Flow ◽  
Flow Mediated Vasodilation ◽  
The Relationship

The muscle metaboreflex is a powerful pressor reflex induced by the activation of chemically sensitive muscle afferents as a result of metabolite accumulation. During submaximal dynamic exercise, the rise in arterial pressure is primarily due to increases in cardiac output, since there is little systemic vasoconstriction. Indeed, in normal animals, we have often shown a small, but significant, peripheral vasodilation during metaboreflex activation, which is mediated, at least in part, by release of epinephrine and activation of vascular β2-receptors. We tested whether this vasodilation is in part due to increased release of nitric oxide caused by the rise in cardiac output eliciting endothelium-dependent flow-mediated vasodilation. The muscle metaboreflex was activated via graded reductions in hindlimb blood flow during mild exercise with and without nitric oxide synthesis blockade [ NG-nitro-l-arginine methyl ester (l-NAME); 5 mg/kg]. We assessed the role of increased cardiac output in mediating peripheral vasodilation via the slope of the relationship between the rise in nonischemic vascular conductance (conductance of all vascular beds excluding hindlimbs) vs. the rise in cardiac output. l-NAME increased mean arterial pressure at rest and during exercise. The metaboreflex-induced increases in mean arterial pressure were unaltered by l-NAME, whereas the increases in cardiac output and nonischemic vascular conductance were attenuated. However, the slope of the relationship between nonischemic vascular conductance and cardiac output was not affected by l-NAME, indicating that the rise in cardiac output did not elicit vasodilation via increased release of nitric oxide. Thus, although nitric oxide is intrinsic to the vascular tonus, endothelial-dependent flow-mediated vasodilation plays little role in the small peripheral vasodilation observed during muscle metaboreflex activation.

Role of vasopressin in blood pressure regulation in conscious water-deprived dogs

1983 ◽  
Vol 244 (1) ◽  
pp. R74-R77 ◽  
Author(s):  
J. Schwartz ◽  
I. A. Reid
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Plasma Renin Activity ◽  
Water Deprivation ◽  
Plasma Renin ◽  
Renin Activity ◽  
Pressure Regulation

The role of vasopressin in the regulation of blood pressure during water deprivation was assessed in conscious dogs with two antagonists of the vasoconstrictor activity of vasopressin. In water-replete dogs, vasopressin blockade caused no significant changes in mean arterial pressure, heart rate, plasma renin activity (PRA), or plasma corticosteroid concentration. In the same dogs following 48-h water deprivation, vasopressin blockade increased heart rate from 85 +/- 6 to 134 +/- 15 beats/min (P less than 0.0001), increased cardiac output from 2.0 +/- 0.1 to 3.1 +/- 0.1 1/min (P less than 0.005), and decreased total peripheral resistance from 46.6 +/- 3.1 to 26.9 +/- 3.1 U (P less than 0.001). Plasma renin activity increased from 12.4 +/- 2.2 to 25.9 +/- 3.4 ng ANG I X ml-1 X 3 h-1 (P less than 0.0001) and plasma corticosteroid concentration increased from 3.2 +/- 0.7 to 4.9 +/- 1.2 micrograms/dl (P less than 0.05). Mean arterial pressure did not change significantly. When the same dogs were again deprived of water and pretreated with the beta-adrenoceptor antagonist propranolol, the heart rate and PRA responses to the antagonists were attenuated and mean arterial pressure decreased from 103 +/- 2 to 91 +/- 3 mmHg (P less than 0.001). These data demonstrate that vasopressin plays an important role in blood pressure regulation during water deprivation in conscious dogs.

Acute and chronic actions of bradykinin on renal function and arterial pressure

1985 ◽  
Vol 248 (1) ◽  
pp. F87-F92 ◽  
Author(s):  
J. P. Granger ◽  
J. E. Hall
Keyword(s):  
Arterial Pressure ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Renal Perfusion ◽  
Acute Effects ◽  
Plasma Aldosterone Concentration ◽  
Control Value ◽  
Renal Vascular

The present study was designed to examine the acute and chronic effects of increased levels of circulating bradykinin (BK) on control of renal hemodynamics, electrolyte excretion, and arterial pressure. Intrarenal infusion of BK (50 ng X kg-1 X min-1) for 60 min in five anesthetized dogs with renal perfusion pressure maintained at a constant level of 108 +/- 1 mmHg had no significant effect on glomerular filtration rate (GFR), whereas it increased renal blood flow (RBF) from a control value of 230 +/- 14 to 282 +/- 18, 266 +/- 15, and 253 +/- 17 ml/min after 15, 30, and 60 min of infusion, respectively. Acute intrarenal infusion of BK also increased urine volume (UV) from 0.255 +/- 0.044 to 0.523 +/- 0.103 ml/min and urinary sodium excretion (UNaV) from 5.72 +/- 1.5 to 13.7 +/- 3.4 mueq/min. To determine whether the potent acute effects of BK on RBF, UV, and UNaV lead to a chronic reduction in arterial pressure, BK (50 ng X kg-1 X min-1) was infused intrarenally for 7 days in conscious dogs. Intrarenal infusion of BK for 7 days had no significant effect on GFR, UNaV, UV, or arterial pressure. However, BK elevated renal plasma flow and decreased renal vascular resistance throughout the 7 days of infusion. Chronic intrarenal BK infusion caused no significant changes in plasma renin activity or plasma aldosterone concentration. Results from these studies indicate that although increased levels of bradykinin in the renal circulation can have potent acute effects on RBF, UV, and UNaV, these effects on UV and UNaV are not sustained and therefore do not result in long-term changes in arterial pressure.

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