Pregnancy prevents hypertensive remodeling and decreases myogenic reactivity in posterior cerebral arteries from Dahl salt-sensitive rats: a role in eclampsia?

Abstract

Aukes AM, Vitullo L, Zeeman GG, Cipolla MJ. Pregnancy prevents hypertensive remodeling and decreases myogenic reactivity in posterior cerebral arteries from Dahl salt-sensitive rats: a role in eclampsia? Am J Physiol Heart Circ Physiol 292: H1071-H1076, 2007. First published October 20, 2006; doi:10.1152 doi:10. /ajpheart.00980.2006ous studies have demonstrated that pregnancy prevents protective hypertension-induced remodeling of cerebral arteries using nitric oxide synthase (NOS) inhibition to raise mean arterial pressure (MAP). In the present study, we investigated whether this effect of pregnancy was specific to NOS inhibition by using the Dahl saltsensitive (SS) rat as a model of hypertension. Nonpregnant (n ϭ 16) and late-pregnant (n ϭ 17) Dahl SS rats were fed either a high-salt diet (8% NaCl) to raise blood pressure or a low-salt diet (Ͻ0.7% NaCl). Third-order posterior cerebral arteries were isolated and pressurized in an arteriograph chamber to measure active responses to pressure and passive remodeling. Several vessels from each group were stained for protein gene product 9.5 to determine perivascular nerve density. Blood pressure was elevated in both groups on high salt. The elevated MAP was associated with significantly smaller active and passive diameters (P Ͻ 0.05) and inward remodeling in the nonpregnant hypertensive group only. Whereas no structural changes were observed in the late-pregnant hypertensive animals, both latepregnant groups had diminished myogenic reactivity (P Ͻ 0.05). Nerve density in both the late-pregnant groups was significantly greater when compared with the nonpregnant groups, suggesting that pregnancy has a trophic influence on perivascular innervation of the posterior cerebral artery. However, hypertension lowered the nerve density in both nonpregnant and late-pregnant animals. It therefore appears that pregnancy has an overall effect to prevent hypertensioninduced remodeling regardless of the mode of hypertension. This effect may predispose the brain to autoregulatory breakthrough, hyperperfusion, and eclampsia when MAP is elevated. gestation; hypertension; brain HYPERTENSION IS ONE OF THE most common complications of pregnancy and is a life-threatening disease for both mother and fetus (27). Several organs are affected by pregnancy-induced hypertension, including the brain manifesting itself as eclampsia with classical neurological features such as headache, nausea, cortical blindness, loss of consciousness, and seizures (35). Eclampsia is one of the leading causes of maternal death (12, 23), yet little is known about how hypertension in pregnancy affects the cerebral circulation and causes the symptoms of eclampsia.The primary explanation for the pathogenesis of eclampsia is that it is thought to be a form of hypertensive encephalopathy (11,22,36,37). This syndrome is characterized by an acute rise in blood pressure that overcomes cerebral artery myogenic tone, causing forced dilatation, autoregulatory breakthrough, and hyperperfusion (21). As a consequence, blood-brain ...

Cerebrovascular Function in Pregnancy and Eclampsia

“…76 Interestingly, it appears that pregnancy has a trophic effect on perivascular innervation of cerebral pial vessels (Figure 3). Aukes et al 88 used a panneuronal stain to show that perivascular innervation of posterior cerebral arteries was increased during pregnancy in the Dahl saltsensitive rat. Because specific neurotransmitters were not quantified, it is not clear what consequence, if any, this finding might have.…”

“…A study that used Dahl salt-sensitive rats made hypertensive by feeding a high-salt diet for the last half of pregnancy (2 weeks) also found that only the nonpregnant rats (treated for the same time period) underwent remodeling, that is, the pregnant animals lacked any structural response to hypertension. 88 The mechanism by which pregnancy prevents hypertensive remodeling of cerebral arteries is not known but appears to be related to the pregnant state. Furthermore, the consequence of pregnancy preventing hypertensive remodeling of cerebral arteries is not clear but may promote forced dilatation at lower pressures and limit the rightward shift in the autoregulatory curve that would normally occur in response to this duration of hypertension.…”

Posterior Reversible Encephalopathy Syndrome: A Rare Complication of Peripartum Pre-eclampsia or Eclampsia- A Case report

“…Pregnancy has direct effects on perivascular innervations by mechanisms not yet elucidated, particularly in pial vessels, in which nerves hypertrophy is produced [15]. This suggests that neurotransmitters may have a role in hypertensive intolerance that results in the genesis of PRES.…”

(−)Doxazosin is a necessary component for the hypotensive effect of (±)doxazosin during long-term administration in conscious rats

“…The proximal occlusion cuff (O-cuff) constricts the tail artery while the distal VPR cuff measures the change in tail artery volume when blood flow resumes as the O-cuff deflates. This system has been validated in a number of studies [14,15,17] . These measurements were performed in a room maintained at 31 °C so as to ensure adequate blood flow through the tail to improve the signal at the VPR transducer.…”

“…In recent years, a new technique for measuring blood pressure in conscious rats using a volume pressure recording system has been validated in a number of studies [14,15] . Longterm oral administration of (±)doxazosin (8 mg/kg for 12 weeks) in the rat was also reported in a study by Yono et al [16] .…”