Hemodynamic Changes Induced by Prolonged NaCl and DOCA Administration in Spontaneously Hypertensive Rats

Chrysant, Steven G.; Walsh, Gerald M.; Fröhlich, Edward D.; Townsend, Susan M.

doi:10.1177/000331977802900406

Cited by 14 publications

(19 citation statements)

References 22 publications

(2 reference statements)

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“…Interestingly, whereas we and others have observed small but significant increases in plasma OSM or Na levels in the DOCA-salt animals compared with Sham-salt controls, [7][8][9][10] in the current study, OSM and Na were insignificantly increased by Ͻ2%. Earlier studies have also failed to detect significant increases in plasma Na concentration (eg, see References [22][23][24] ). Yet, despite the small magnitude, our data clearly suggest that these extremely small, at times undetectable, elevations in OSM are sufficient to produce hypertension.…”

Section: Discussionmentioning

confidence: 99%

Central Action of Increased Osmolality to Support Blood Pressure in Deoxycorticosterone Acetate–Salt Rats

O'Donaughy

Brooks

2006

Hypertension

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Abstract-To test the hypothesis that increased osmolality contributes to hypertension in deoxycorticosterone acetate (DOCA)-salt-hypertensive rats by acting in the brain, DOCA-salt and Sham-salt rats were instrumented with bilateral, nonoccluding intracarotid and femoral catheters. Two weeks prior, rats were uninephrectomized and received subcutaneous implants with or without DOCA (65 mg) and began drinking salt water (1% NaCl and 0.2% KCl). DOCA-salt rats (nϭ28) exhibited elevated blood pressure (159Ϯ4 mm Hg; PϽ0.05) and heart rate (392Ϯ10 bpm; PϽ0.05) compared with Sham-salt animals (nϭ5; blood pressure: 107Ϯ5 mm Hg; heart rate: 355Ϯ10 bpm). Bilateral intracarotid infusion of hypotonic fluid (osmolality: Ϸ40 mOsm/L), which lowers osmolality of blood to the brain by Ϸ2%, rapidly decreased blood pressure in DOCA-salt rats (Ϫ22Ϯ4 mm Hg after 15 minutes; PϽ0.05; nϭ7) but not Sham-salt rats (2Ϯ2 mm Hg; nϭ5). Hypotonic fluid infused intravenously did not lower blood pressure (0Ϯ2 mm Hg) in DOCA-salt rats (nϭ7). In DOCA-salt rats pretreated with a V 1 vasopressin antagonist (Manning compound, 5 g, IV), intracarotid hypotonic infusion still decreased blood pressure (Ϫ10Ϯ3 mm Hg; PϽ0.05; nϭ9), but the response was smaller (PϽ0.05). Finally, in DOCA-salt rats (nϭ4) pretreated with the V 1 antagonist and the ganglionic blocker hexamethonium, decreasing osmolality of blood to the brain did not reduce blood pressure. These data indicate that, in DOCA-salt rats, hypertonicity acts in the brain to support blood pressure, in part by stimulating vasopressin secretion and in part by stimulating another rapidly reversible mechanism, likely the sympathetic nervous system. Key Words: hypertension, sodium-dependent Ⅲ central nervous system Ⅲ hypertension, mineralocorticoid Ⅲ sodium Ⅲ sympathetic nervous system Ⅲ vasopressin I ncreasing evidence supports a role for body fluid osmolality (OSM) in the regulation of blood pressure (BP) and sympathetic nerve activity (for reviews see References 1,2 ). Acute increases in OSM rapidly elevate BP and sympathetic nerve activity to specific beds, 3-5 and more chronic increases in plasma OSM, such as during water deprivation, seem to sustain this rapid sympathoexcitation. 6 Moreover, recent studies suggest that increased OSM contributes to sympathoexcitation in at least one model of salt-sensitive hypertension, the deoxycorticosterone-treated rat consuming excess salt (DOCA-salt) rat. More specifically, DOCA-salt rats exhibit hypertension and elevated OSM and/or NaCl levels, 7-10 and normalization of OSM results in profound decreases in BP and lumbar sympathetic nerve activity. 8 However, the site at which OSM is sensed to trigger sustained sympathoexcitation in DOCA-salt rats has not been identified.Osmoreceptors are present in numerous organs, including the liver, kidney, and brain, but significant indirect evidence implicates the brain in this action. First, forebrain circumventricular organs contain osmoreceptors that are exquisitely sensitive to minute changes in OSM. 11 Second, forebrain...

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Section: Discussionmentioning

confidence: 99%

Central Action of Increased Osmolality to Support Blood Pressure in Deoxycorticosterone Acetate–Salt Rats

O'Donaughy

Brooks

2006

Hypertension

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“…10,11 Although some investigators have believed that the SHR was not salt-sensitive, our findings (and those of others) have clearly demonstrated that these genetically hypertensive rats are, indeed, salt-sensitive. 12,13 Moreover, when desoxycorticosterone acetate was added to salt-loading, malignant hypertension developed. 12 Thus, in contrast with their normotensive Wistar-Kyoto (WKY) controls that responded to long-term salt-loading with increased cardiac output but unchanged arterial pressure, the SHR demonstrated increased arterial pressure and total peripheral resistance and a normal cardiac output (and, hence, a normal ventricular preload was associated with salt-loading).…”

Section: Personal Investigative and Other Supportive Evidencementioning

confidence: 99%

“…12,13 Moreover, when desoxycorticosterone acetate was added to salt-loading, malignant hypertension developed. 12 Thus, in contrast with their normotensive Wistar-Kyoto (WKY) controls that responded to long-term salt-loading with increased cardiac output but unchanged arterial pressure, the SHR demonstrated increased arterial pressure and total peripheral resistance and a normal cardiac output (and, hence, a normal ventricular preload was associated with salt-loading). 13 We followed these reports with another study in which long-term low, normal, or 4% saltloading diets were administered to separate groups of SHR.…”

Section: Personal Investigative and Other Supportive Evidencementioning

confidence: 99%

The Salt Conundrum

Fröhlich

2007

Hypertension

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Section: Introductionmentioning

confidence: 99%

“…exposed to high sodium intake over long periods of time aggravate their hypertension [2,[6][7][8]12] and they may even develop malignant hypertension [2,8,12]. These adverse effects of sodium on the arterial pressure of these rats are mediated through an elevation of peripheral vascular resistance [6,7], Tobian et al [27] have demonstrated that high sodium intake by the salt-sensitive Dahl rats resuited in reduction of prostaglandin concentration in their renal tissue. The kidney is the major producer of E prostaglandins and these substances have been shown to play an important role in blood pressure regulation through local vasodilation and sodium excretion by the kidney [5,11,15,26], Dunn [9] has reported that the kidneys of SHR increase the production of all prostaglandins with time, possibly, in an attempt to arrest the progression of hypertension.…”

Section: Introductionmentioning

confidence: 99%

Renal Functional and Organic Changes Induced by Salt and Prostaglandin Inhibition in Spontaneously Hypertensive Rats

Chrysant

Mandal

Nordquist³

1980

Nephron

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The prolonged (3 months) effects of high sodium intake and sodium meclofenamate were studied in two groups of male spontaneously hypertensive rats. Group 1 (8 rats) received 1% NaCl in tap water ad libitum and served as control. Group 2 (8 rats) received, besides 1 % NaCl in tap water, 50 µg/ml of sodium meclofenamate per rat daily. Renal metabolic, hemodynamic and histologic studies were done at the end of the study. The renal functional studies were performed in the unanesthetized, unrestrained state. Group 2 rats developed significantly higher arterial pressures, renal vascular resistance and histologic changes (p < 0.005), larger left ventricular weights (p < 0.05) and significantly lower effective renal plasma flow, renal blood flow (p < 0.005) and glomerular filtration rate (p < 0.05) than group 1 rats. There were no differences between the two groups of rats with respect to heart rate, hematocrit, right ventricular weight, body weight, fluid intake, urine output, sodium and potassium excretion and serum electrolytes. The results suggest that the combination of high sodium intake and prostaglandin synthesis inhibition exert a greater damaging effect on the arterial pressure and renal function of spontaneously hypertensive rats than salt alone.

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Hemodynamic Changes Induced by Prolonged NaCl and DOCA Administration in Spontaneously Hypertensive Rats

Cited by 14 publications

References 22 publications

Central Action of Increased Osmolality to Support Blood Pressure in Deoxycorticosterone Acetate–Salt Rats

Central Action of Increased Osmolality to Support Blood Pressure in Deoxycorticosterone Acetate–Salt Rats

The Salt Conundrum

Renal Functional and Organic Changes Induced by Salt and Prostaglandin Inhibition in Spontaneously Hypertensive Rats

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