Pregnancy Prevents Hypertensive Remodeling of Cerebral Arteries

Abstract

Abstract-We investigated how hypertension during pregnancy affected passive structural (wall:lumen, wall stress) and active (myogenic activity) responses of the cerebral circulation. Female nonpregnant (NP; nϭ8) Sprague Dawley rats were compared with late-pregnant (LP; day 19 to 20, nϭ6) rats. Some animals were treated with the NO synthase inhibitor nitro-L-arginine in their drinking water to raise blood pressure. LP rats (nϭ6) were treated for the last 7 days of pregnancy (last trimester) to mimic preeclampsia and compared with NP rats treated for the same duration (nϭ8). Active and passive responses were determined on isolated and pressurized third-order posterior cerebral arteries. Nitro-L-arginine treatment significantly raised blood pressure in both groups of animals that was associated with increased wall thickness and wall:lumen ratio in the NP hypertensive animals versus controls (PϽ0.05). In contrast, this response to pressure was absent in LP animals, which had similar wall measurements. In addition, arteries from NP hypertensive animals had increased myogenic tone and pressure of forced dilatation compared with NP control animals (PϽ0.01). Again, this response was lacking in the LP hypertensive animals that had similar tone and pressure of forced dilatation as normotensive controls. The increased tone and wall thickness decreased wall stress in the NP hypertensive animals, a response that did not occur in LP hypertensive animals. Because medial hypertrophy is considered a protective response to elevated blood pressure, these results suggest that hypertension in pregnancy may predispose the cerebral circulation to autoregulatory breakthrough and blood-brain-barrier disruption when blood pressure is elevated, as during eclampsia. Key Words: hypertension, pregnancy Ⅲ cerebral arteries Ⅲ pregnancy Ⅲ eclampsia Ⅲ hypertrophy T he neurological complications of eclampsia are thought to be similar to hypertensive encephalopathy in which an acute, excessive elevation in pressure causes forced dilatation of cerebral artery myogenic tone, autoregulatory breakthrough, and edema formation. 1-3 Our previous work demonstrated that normal pregnancy may predispose the brain to eclampsia by lowering the pressure at which forced dilatation of cerebral arteries occurs. 4 Whereas this effect may not be consequential if mean arterial pressure remains within the normal autoregulatory pressure range, it may cause bloodbrain barrier (BBB) disruption and edema formation if pressure is elevated, as during hypertension in pregnancy and preeclampsia/eclampsia.It is now established that chronic hypertension is associated with medial hypertrophy of both large and small cerebral arteries that increases the wall:lumen ratio. [5][6][7][8][9] This response of the cerebrovascular smooth muscle to chronically elevated blood pressure is considered to be an important protective function. 6 Several studies have shown that spontaneously hypertensive rats 10,11 and stroke-prone spontaneously hypertensive rats 12 were less susceptible to BBB di...

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

“…1A and 2A). This inward remodeling of cerebral arteries has been shown in numerous other studies using genetically hypertensive male animals (1, 16) and during L-NAME hypertension in female animals (7,24). To our knowledge, this is the first study to specifically show this response to hypertension in cerebral arteries from female Dahl SS animals.…”

“…Hypertension during pregnancy is not quite chronic hypertension, but more a unique form of hypertension, because it is somewhere between chronic and acute. Yet, vascular remodeling occurs quickly after the onset of hypertension; after only 7 days of L-NAME treatment, the PCAs of pregnant SpragueDawley rats showed significant vascular remodeling (7).…”

“…Blood pressures were measured every day by a tail-cuff method using the Coda 6 System (Kent Scientific), as previously described (7). The volume and pressurerecording technique allowed noninvasive measurements of six blood pressure parameters: systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, tail blood volume, and tail blood flow.…”

“…One study in which N G -nitro-L-arginine methyl ester (L-NAME) was used to raise mean arterial pressure in nonpregnant (NP) and late-pregnant (LP) Sprague-Dawley rats demonstrated significant remodeling and medial hypertrophy of the posterior cerebral artery (PCA) from NP animals, a response that was absent in the LP animals (7). In addition, LP animals underwent forced dilatation at significantly lower pressures compared with NP animals, regardless of the presence of hypertension.…”

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

“…[1][2][3][4][5][6][7][8][9][10][11] These alterations in vascular function not only lead to hypertension but multi-organ dysfunction, especially in women with early onset preeclampsia. 1,4,[11][12][13][14][15][16][17][18][19][20] Preterm preeclampsia remains a leading cause of maternal death and perinatal morbidity. Moreover, it has recently been recognized that women who endure preeclampsia are at a greater risk for cardiovascular disease later in life.…”