Effects of Centrally Administered Losartan on Deoxycorticosterone-salt Hypertension Rats

Park, Chang Gyu; Leenen, Frans H. H.

doi:10.3346/jkms.2001.16.5.553

Cited by 48 publications

(42 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[23][24][25][26] Consistent with our hypothesis, we found that induction of a hypertensive state was associated with a decrease in the levels of hypothalamic ␥-adducin. However, in contrast to genetic models, ␥-adducin levels in the brainstem did not change in both nongenetic rat models.…”

Section: Discussionsupporting

confidence: 88%

Decrease in Hypothalamic Gamma Adducin in Rat Models of Hypertension

et al. 2004

View full text Add to dashboard Cite

Abstract-We have previously shown that a decrease in hypothalamic gamma adducin (␥-adducin) is associated with hypertension in the spontaneously hypertensive rat (SHR). In view of many inherent issues with SHR, our objective in the present study was to provide proof of this concept with the use of 2 nongenetic rat models of hypertension. Subcutaneous angiotensin II (Ang II) infusion for 2 weeks (55 ng/kg per day) resulted in an increase in blood pressure (BP) of 18 mm Hg. This was associated with a 70% decrease in hypothalamic ␥-adducin. Concomitant administration of losartan attenuated the development of hypertension and a decrease in ␥-adducin. Deoxycorticosterone acetate salt-induced hypertension also caused a 70% decrease in hypothalamic ␥-adducin. Finally, neuronal cultures from neonatal rat brains were incubated with 100 nmol/L Ang II for 4 hours to mimic the in vivo Ang II infusion rat model. This chronic incubation with Ang II resulted in a 60% decrease in the neuronal ␥-adducin. Taken together, these observations strengthen our hypothesis that a decrease in hypothalamic ␥-adducin is linked to hypertension. Key Words: angiotensin Ⅲ hypertension Ⅲ brain Ⅲ hypothalamus T he central nervous system (CNS) plays a critical role in the control of many cardiovascular functions by regulating such physiological mechanisms as sympathetic nerve activity, vasopressin release, and baroreceptor reflexes. 1,2 Dysregulation of one or more of these physiological pathways is associated with the development and maintenance of hypertension. [2][3][4] For example, an increased sympathetic nerve activity that is linked to animal models and human hypertension has been identified as one of the key physiological mechanisms that is altered in neurogenic hypertension. 2 Despite abundant evidence supporting dysregulated CNS function, the therapeutic potential of these findings in the control and treatment of neurogenic hypertension has not been fully explored. In part, this may be because of the fact that little is known about the cellular and molecular basis of this alteration in hypertension.Our research group has been involved in filling this important gap in knowledge by identifying and characterizing genes and signaling pathways that are uniquely altered in the brain of the spontaneously hypertensive rat (SHR). 2,5 These studies have demonstrated that the expression of gammaadducin (␥-adducin), a cytosolic protein, is reduced in the hypothalamic-brainstem areas of the SHR. 6 ␥-Adducin belongs to a family of cytosolic proteins whose dimerization with an ␣ isoform plays a critical role in the control of cytoskeletal-mediated cellular processes. 7 For example, ␣/␥ heterodimers of adducin have been demonstrated to regulate protein kinases involved in vesicular trafficking, calcium mobilization, and transmitter release. 7 In addition, its interaction with Na ϩ /K ϩ ATPase regulates the pump activity and thus regulates neuronal activity. 8,9 These observations, together with our data on ␥-adducin expression, lead us to propose that a...

show abstract

Section: Discussionsupporting

confidence: 88%

Decrease in Hypothalamic Gamma Adducin in Rat Models of Hypertension

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Porter et al have demonstrated that ICV infusion of angiotensin II causes increased energy expenditure in both young and old rats [31,32]. Chronic delivery of DOCA-salt results in hypertension that depends upon increased activity of the brain RAS, as ICV infusion of the ACE inhibitor captopril or the AT1 antagonist losartan prevent and reverse DOCA-salt hypertension [71][72][73]. Similarly, ICV infusion of losartan attenuates the resting metabolic rate increase that occurs with DOCA-salt [74].…”

Section: The Brain Ras and Energy Outputmentioning

confidence: 91%

Control of Energy Balance by the Brain Renin-Angiotensin System

Claflin

Grobe

2015

Curr Hypertens Rep

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) exists as a circulating hormone system but it is also used by various tissues of the body, including the brain, as a paracrine signaling mechanism. The local brain version of the RAS is mechanistically involved in fluid balance and blood pressure control, and there is growing appreciation for a role of the brain RAS in the control of energy balance. Here, we review major evidence for the control of energy balance by the brain RAS; outline the current understanding of the RAS components, targets, and mechanisms involved; and highlight some major questions that currently face the field.

show abstract

“…The DOCA-salt model (deoxycorticosterone acetate plus a high dietary sodium load) of hypertension is a well-established model of low-renin hypertension mechanistically involving brain ANG II and AT 1A receptors (16)(17)(18). It is notable that DOCAsalt also robustly stimulates RMR, an effect that also requires brain AT 1A receptors (19).…”

Section: Resultsmentioning

confidence: 99%