Effect of lesions of the anteroventral third ventricle (AV3V) on the development of hypertension in spontaneously hypertensive rats.

Gordon, Frank J.; Haywood, Joseph R.; Brody, Michael J.; Johnson, Alan Kim

doi:10.1161/01.hyp.4.3.387

Cited by 46 publications

(23 citation statements)

References 16 publications

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“…25,26 The AV3V area seems to function differently in SHR. As shown by Brody and colleagues, 25,27,28 lesions placed in this region interfered with several different forms of hypertension in rats 27,28 (DOCA-salt, Goldblatt, and Dahl salt-sensitive rats) but, by contrast, failed to affect the development or maintenance of hypertension in SHR. In SHR, the lesion of the AV3V region caused adipsia and the loss of pressor and dipsogenic responses to centrally administered angiotensin II, similar to what is observed in other rat strains.…”

Section: Discussionmentioning

confidence: 82%

“…However, electrical stimulation of the AV3V region in intact SHR caused smaller vasoconstrictor and vasodilator responses than observed in WKY, with a much smaller pressor response in SHR than in WKY. 27,28 Brody et al 28 suggested that the interrupted reflex arc that originates with renal afferent activation may be the base of the prevention of different forms of hypertension by the AV3V lesion. We postulate that the observed absence of response to central MR blockade in SHR depends on a dysfunction of the AV3V region.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of Brain Mineralocorticoid Receptor in Salt-Enhanced Hypertension in Spontaneously Hypertensive Rats

et al. 2001

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Abstract-We recently showed that brain mineralocorticoid receptors (MRs) are involved in blood pressure and kidney function control in normotensive Wistar rats. We now assessed the involvement of brain MRs in spontaneously hypertensive rats (SHR), in which the presence of adrenocorticoids has been shown to be required for the development of hypertension. The effect of a single intracerebroventricular (ICV) injection of an MR antagonist (RU28318) on systolic blood pressure (SBP) and renal function was examined in conscious adult SHR and Wistar-Kyoto rats (WKY) maintained on a standard-sodium diet (0.4% Na ϩ ). In WKY, a long-lasting decrease in SBP was caused by the ICV injection of 10 ng RU28318 as previously reported in Wistar rats, associated with increased urinary excretion of water and electrolytes. In SHR maintained on the standard diet, the ICV injection of RU28318 (10 or 100 ng) had no effect on cardiovascular and renal functions. However, the ICV injection of 10 ng RU28318 in SHR after 3 weeks of high sodium intake (8% Na ϩ ) caused a long-lasting decrease in SBP. The effect was present at 8 hours (⌬SBP 34Ϯ2 mm Hg), persisted at 24 hours (⌬SBP 29Ϯ1 mm Hg), and disappeared at 48 hours after the injection. The hypotension was not associated with changes in heart rate, urinary excretion of water and electrolytes, and plasma renin activity, whereas renal denervation did not affect the decrease in SBP. A more pronounced decrease in SBP (49Ϯ3 mm Hg at 8 hours) was observed with 100 ng RU28318. This dose of the antagonist was without effect after subcutaneous administration. Key Words: brain Ⅲ mineralocorticoids Ⅲ rats, inbred SHR Ⅲ sodium Ⅲ rats, inbred WKY S everal lines of evidence suggest that brain mineralocorticoid receptors (MRs) are involved in blood pressure control in hypertension induced by mineralocorticoids but also appear to play a role in cardiovascular control in normotensive animals. [1][2][3][4] In normotensive Wistar rats, we recently showed that selective blockade of brain MRs induced a long-lasting decrease in blood pressure associated with increased diuresis and augmented urinary excretion of electrolytes. 4 The involvement of brain MRs in hypertension was demonstrated in deoxycorticosterone (DOCA)-salt rats as well as in genetic hypertension in Dahl salt-sensitive rats. Intracerebroventricular (ICV) infusion of an MR antagonist inhibited the rise in blood pressure induced by DOCA-salt as well as the development of salt-dependent hypertension in Dahl salt-sensitive rats. 2,5 For spontaneously hypertensive rats (SHR), data are lacking regarding a role of brain MRs in the development or maintenance of hypertension, except for a brief report suggesting refractoriness to high doses of an MR antagonist administered ICV in adult SHR. 6 The pathophysiology of the development of hypertension in SHR so far has not been resolved. However, evidence is substantial for a role of brain mechanisms that cause an early increase in sympathetic nervous activity. 7-9 SHR show enhanced pressor responses to a v...

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Involvement of Brain Mineralocorticoid Receptor in Salt-Enhanced Hypertension in Spontaneously Hypertensive Rats

et al. 2001

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“…Immunostaining has provided biochemical evidence that NOS in the PVN is downregulated in the spontaneously hypertensive rat (SHR), a chronic heart failure rat model, a diabetic rat model, and a diet-induced obesity rat model (1,11,30,34,39,45,48,49,51). In addition, in two chronic models of hypertensive rats, central mineralocorticoid-induced hypertension and chronic renal failure, a significant decrease in the amount of nNOS mRNA was found in the hypothalamus and rostral and caudal ventrolateral medulla (39,45).…”

Section: Discussionmentioning

confidence: 99%

“…ROS production is increased in human and experimental hypertension and, moreover, plays an important role in blood pressure regulation (3,18,23,38). In the brain, ROS are recognized for their involvement in neurodegenerative diseases, but they have recently been implicated in modulating blood pressure and sympathetic nerve activity (4,10,11,35,47,50). In addition, recent observations in cardiac myocytes have demonstrated a unique interaction between NOS and superoxide such that a deficiency of nNOS leads to a profound increase in xanthine oxidoreductase-mediated superoxide production (19).…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide synthase, ADMA, SDMA, and nitric oxide activity in the paraventricular nucleus throughout the etiology of renal wrap hypertension

Northcott

Billecke²,

Craig

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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LG, Haywood JR. Nitric oxide synthase, ADMA, SDMA, and nitric oxide activity in the paraventricular nucleus throughout the etiology of renal wrap hypertension. Am J Physiol Heart Circ Physiol 302: H2276 -H2284, 2012. First published March 23, 2012; doi:10.1152/ajpheart.00562.2011.-Within the paraventricular nucleus (PVN), there is a balance between the excitatory and inhibitory neurotransmitters that regulate blood pressure; in hypertension, the balance shifts to enhanced excitation. Nitric oxide (NO) is an atypical neurotransmitter that elicits inhibitory effects on cardiovascular function. We hypothesized that reduced PVN NO led to elevations in blood pressure during both the onset and sustained phases of hypertension due to decreased NO synthase (NOS) and increased asymmetrical dimethylarginine (ADMA; an endogenous NOS inhibitor) and symmetric dimethylarginine (SDMA). Elevated blood pressure, in response to PVN bilateral microinjections of a NO inhibitor, nitro-L-arginine methyl ester, was blunted in renal wrapped rats during the onset of hypertension (day 7) and sustained renal wrap hypertension (day 28) compared with sham-operated rats. Adenoviruses (Ad) encoding endothelial NOS (eNOS) or LacZ microinjected into the PVN [1 ϫ 10 9 plaque-forming units, bilateral (200 nl/site)] reduced mean arterial pressure compared with control (Day 7, Ad LacZ wrap: 144 Ϯ 7 mmHg and Ad eNOS wrap: 117 Ϯ 5 mmHg, P Յ 0.05) throughout the study (Day 28, Ad LacZ wrap: 123 Ϯ 1 mmHg and Ad eNOS wrap: 108 Ϯ 4 mmHg, P Յ 0.05). Western blot analyses of PVN NOS revealed significantly lower PVN neuronal NOS during the onset of hypertension but not in sustained hypertension. Reduced SDMA was found in the PVN during the onset of hypertension; however, no change in ADMA was observed. In conclusion, functional indexes of NO activity indicated an overall downregulation of NO in renal wrap hypertension, but the mechanism by which this occurs likely differs throughout the development of hypertension. asymmetrical dimethylarginine; symmetrical dimethylarginine; neurotransmission; gene transfer THE PARAVENTRICULAR NUCLEUS (PVN) of the hypothalamus contains a heterogeneous cell population that participates in a multitude of physiological functions, including the regulation of blood pressure. Pathways descending from the PVN project to the rostral ventrolateral medulla and/or preganglionic sympathetic neurons in the spinal cord. These pathways control sympathetic nerve activity and blood pressure. Both excitatory and inhibitory neurotransmitters are released within the PVN, with a summation of their actions influencing neuronal activity in the descending pathways and, ultimately, blood pressure. During hypertension, the balance between excitatory and inhibitory neurotransmitters is shifted to increased excitation, resulting in increases in blood pressure and hypertension. Thus far, the temporal neurochemical changes that occur in the hypertensive process have received limited attention. By further understanding the development of hypertension, we...

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“…Although lesion of the AV3V region attenuates blood pressure in many forms of experimental hypertension, 22 destruction of this area appears not to alter the course of hypertension in SHR. 34 Thus, if the AV3V tissue is not necessary for the expression of hypertension in SHR, then it follows that the increased angiotensinogen gene expression found in this area is not a necessary prerequisite for the hypertensive phenotype. Of course this does not mean that brain areas that lie outside of the AV3V region and express elevated angiotensinogen mRNA are unrelated to the hypertensive phenotype in SHR.…”

Section: Discussionmentioning

confidence: 99%

Brain and liver angiotensinogen messenger RNA in genetic hypertensive and normotensive rats.

et al. 1991

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The brain's renin-angiotensin system is integrally involved in the regulation of blood pressure and fluid/mineral metabolism. Enhanced activity of the angiotensin system in the brain has been implicated as a possible source of the hypertension and the elevated salt appetite of the spontaneously hypertensive rat, as compared with the Wistar-Kyoto rat This study tested whether these inbred strains of hypertensive and normotensive rats differ in central or peripheral expression of the gene coding for angiotensinogen, the prohormone for the angiotensin peptides. Angiotensinogen messenger RNA was measured in the brain by in situ hybridization and in the liver by Northern blot analysis, using a synthetic oligonucleotide. There was a 28% greater expression of the angiotensinogen gene in the region of the anteroventral hypothalamus, preoptic area, and medial septum of the hypertensive strain. There were no differences between strains in liver angiotensinogen gene expression. These results are consistent with the possibility that enhanced elaboration of the angiotensin prohormone in the brain contributes, in part, to the hypertension or the elevated salt appetite of the spontaneously hypertensive rat (Hypertension 1991;17:485-491) T he inbred spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat strains express distinct cardiovascular and behavioral phenotypes that make them useful models for the study of hypertension. Although derived from the same progenitor strain, the SHR are hypertensive and salt-avid, whereas the WKY rats are normotensive and exhibit a substantially lower appetite for saline solutions.'-4 The brain's renin-angiotensin system is integrally involved in the regulation of blood pressure and aspects of fluid/mineral metabolism,

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Effect of lesions of the anteroventral third ventricle (AV3V) on the development of hypertension in spontaneously hypertensive rats.

Cited by 46 publications

References 16 publications

Involvement of Brain Mineralocorticoid Receptor in Salt-Enhanced Hypertension in Spontaneously Hypertensive Rats

Involvement of Brain Mineralocorticoid Receptor in Salt-Enhanced Hypertension in Spontaneously Hypertensive Rats

Nitric oxide synthase, ADMA, SDMA, and nitric oxide activity in the paraventricular nucleus throughout the etiology of renal wrap hypertension

Brain and liver angiotensinogen messenger RNA in genetic hypertensive and normotensive rats.

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