Deficient production of nitric oxide induces volume-dependent hypertension

Lahera, V.; Salazar, J; Salom, Miguel G.; Romero, J. C.

doi:10.1097/00004872-199212000-00019

Cited by 41 publications

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“…Two other groups reported simultaneously or soon thereafter the development of hypertension associated with chronic L-NAME treatment. 29,30 These findings, subsequently confirmed by other researchers, indicated that NO is a fundamental and irreplaceable element in the regulation of BP and gave birth to a new model of arterial hypertension.…”

Section: Development Of the Chronic Nos Inhibition Modelmentioning

confidence: 56%

“…Indeed, Fujihara et al 51 and Tolins and Schultz 86 showed that administration of a high salt diet aggravated hypertension and renal injury in rats given chronic treatment with L-NAME. Conversely, Romero et al 30,87 showed that dietary salt restriction completely prevented development of hypertension in this model. Nevertheless, other investigators observed no impact of varying salt intake on L-NAME-induced hypertension.…”

Section: Role Of Salt Retentionmentioning

confidence: 86%

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Chronic Nitric Oxide Inhibition Model Six Years On

1998

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Keywords models; cardiovascular diseases; nitric oxide synthase; nitric oxide; blood pressure; reninangiotensin system; vasodilationThe discovery in 1987 that endothelium-derived nitric oxide (NO) mediates the vasodilatory effect of certain endothelium-dependent agonists 1,2 inaugurated the current huge field of NO biology. It is now recognized that NO plays essential roles in many diverse physiological processes and in some pathophysiologic events. Development of these concepts has been based largely on evidence obtained by limiting NO biosynthesis. This review is centered on the cardiovascular and particularly the renal functional and structural consequences of chronic pharmacologic NO inhibition by L-arginine analogues. We devoted special attention to the mechanisms of hypertension and organ injury that occur under these circumstances, while appreciating the inherent limitations surrounding interpretation of this data. Ubiquity and Heterogeneity of NO BiosynthesisNO is made by the enzymatic action of several widely distributed NO synthases (NOS). In the presence of the substrates L-arginine and oxygen, as well as a number of essential cofactors, NO is produced in response to appropriate stimuli. The constitutively expressed NOS play a major role in the physiological control of vascular tone and kidney function. 3,4 Vascular endothelial NOS (eNOS) and brain-type NOS (bNOS) are widely distributed throughout the kidney 5 as well as the cardiovascular system and in strategic locations in the peripheral and central nervous system (CNS). 6,7 Both eNOS and particularly bNOS are abundant in the kidney, glomeruli, and vasculature as well as in most segments of the tubule, 3,5 and NOS activity in medulla is considerably greater than in cortex. 8 NO generated within the kidney controls the glomerular filtration rate (GFR), total renal and medullary blood flow, pressure natriuresis, epithelial sodium transport, and production of various vasoactive factors including renin. 3-5 eNOS is distributed throughout most parts of the arterial and venous circulation, although there is considerable heterogeneity in the extent to which NO controls tone in regional circulations. 9 Although there is some basal NO release from eNOS, shear stress is the physiologically important regulator of vascular NO production. 3 In the CNS, NO is made in the nucleus tractus solitarius, the paraventricular nucleus, and the ventral medulla and can control sympathetic outflow. 6,10 In addition to central regulation of efferent renal sympathetic nerve activity, there is direct nitrergic innervation to several locations including the renal vasculature. 7

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Section: Development Of the Chronic Nos Inhibition Modelmentioning

confidence: 56%

Section: Role Of Salt Retentionmentioning

confidence: 86%

Chronic Nitric Oxide Inhibition Model Six Years On

1998

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“…Key Words: vasomotor system Ⅲ rostral ventrolateral medulla Ⅲ hypertension, experimental Ⅲ L-NAME Ⅲ glutamate I t is well known that pharmacological inhibition of nitric oxide synthase (NOS) produces acute and chronic hypertension, but the mechanisms mediating the hypertension are not completely understood. [1][2][3][4][5] Although this hypertension was first attributed solely to inhibition of endothelial nitric oxide (NO), more recently a large body of evidence suggests the involvement of the central nervous system. In particular, inhibition of neuronal NO may contribute to the hypertension induced by long-term treatment with N G -nitro-L-arginine methyl ester (L-NAME).…”

mentioning

confidence: 99%

“…[1][2][3][4][5] Although this hypertension was first attributed solely to inhibition of endothelial nitric oxide (NO), more recently a large body of evidence suggests the involvement of the central nervous system. In particular, inhibition of neuronal NO may contribute to the hypertension induced by long-term treatment with N G -nitro-L-arginine methyl ester (L-NAME).…”

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confidence: 99%

Rostral Ventrolateral Medulla

1999

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Abstract-The major aim of the present study was to evaluate the role of the rostral ventrolateral medulla (RVLM) in the maintenance of hypertension in rats subjected to long-term treatment with N G -nitro-L-arginine methyl ester (L-NAME) (70 mg/kg orally for 1 week). We inhibited or stimulated RVLM neurons with the use of drugs such as glycine, L-glutamate, or kynurenic acid in urethane-anesthetized rats (1.2 to 1.4 g/kg IV). Bilateral microinjection of glycine (50 nmol, 100 nL) into the RVLM of hypertensive rats produced a decrease in mean arterial blood pressure (MAP) from 158Ϯ4 to 71Ϯ4 mm Hg (PϽ0.05), which was similar to the decrease produced by intravenous administration of hexamethonium. In normotensive rats, glycine microinjection reduced MAP from 106Ϯ4 to 60Ϯ3 mm Hg (PϽ0.05). Glutamate microinjection into the RVLM produced a significant increase in MAP in both hypertensive rats (from 157Ϯ3 to 201Ϯ6 mm Hg) and normotensive rats (from 105Ϯ5 to 148Ϯ9 mm Hg). No change in MAP was observed in response to kynurenic acid microinjection into the RVLM in either group. These results suggest that hypertension in response to long-term L-NAME treatment is dependent on an increase in central sympathetic drive, mediated by RVLM neurons. However, glutamatergic synapses within RVLM are probably not involved in this response. Key Words: vasomotor system Ⅲ rostral ventrolateral medulla Ⅲ hypertension, experimental Ⅲ L-NAME Ⅲ glutamate I t is well known that pharmacological inhibition of nitric oxide synthase (NOS) produces acute and chronic hypertension, but the mechanisms mediating the hypertension are not completely understood. [1][2][3][4][5] Although this hypertension was first attributed solely to inhibition of endothelial nitric oxide (NO), more recently a large body of evidence suggests the involvement of the central nervous system. In particular, inhibition of neuronal NO may contribute to the hypertension induced by long-term treatment with N G -nitro-L-arginine methyl ester (L-NAME). 6 -8 Contradictory results have been reported about the role of the sympathetic nervous system (SNS) in the maintenance of hypertension induced by NOS blockade. In some studies, blockade of the SNS had no effect on this hypertension, 9,10 whereas other studies using similar methods showed a significant reduction in hypertension. 6,8,11 Because the rostral ventrolateral medulla (RVLM) contains sympathetic premotor neurons and is considered to be the final common pathway for several cardiovascular responses and for the control of sympathetic vasomotor tone, it is reasonable to suggest that these premotor neurons may be involved in the maintenance of hypertension due to NOS inhibition. 12 To test this hypothesis, we performed a study in which we compared the effects of pharmacological inhibition of the RVLM with the effects of ganglionic blockade on mean arterial pressure (MAP) and heart rate (HR) in hypertensive and control groups. We also tested the role of glutamatergic synapses within the RVLM in this model. MethodsExperiments wer...

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“…The primary receptor for NO is soluble guanylate cyclase producing cGMP in the target cells (9). Interestingly, cGMP production in response to ACh or NO-donors in the kidney has been found most prominently in the renal medulla (21).…”

Section: Armin Justmentioning

confidence: 99%

Salt control. Focus on “High salt induces autocrine actions of ET-1 on inner medullary collecting duct NO production via upregulated ET_B receptor expression”

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2016

American Journal of Physiology-Regulatory, Integrative and Comp

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Deficient production of nitric oxide induces volume-dependent hypertension

Cited by 41 publications

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Chronic Nitric Oxide Inhibition Model Six Years On

Chronic Nitric Oxide Inhibition Model Six Years On

Rostral Ventrolateral Medulla

Salt control. Focus on “High salt induces autocrine actions of ET-1 on inner medullary collecting duct NO production via upregulated ET_B receptor expression”

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Deficient production of nitric oxide induces volume-dependent hypertension

Cited by 41 publications

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Chronic Nitric Oxide Inhibition Model Six Years On

Chronic Nitric Oxide Inhibition Model Six Years On

Rostral Ventrolateral Medulla

Salt control. Focus on “High salt induces autocrine actions of ET-1 on inner medullary collecting duct NO production via upregulated ETB receptor expression”

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Salt control. Focus on “High salt induces autocrine actions of ET-1 on inner medullary collecting duct NO production via upregulated ET_B receptor expression”