Impact of the renin‐angiotensin system on cerebral perfusion following subarachnoid haemorrhage in the rat

Abstract

Subarachnoid haemorrhage (SAH) is a serious condition characterized by a high level of morbidity and mortality. Indeed, some studies have documented the mortality to be as high as 45 % in the 30 days following the trauma (Broderick et al. 1994). Despite improved microsurgical techniques this high level of mortality remains, largely as a consequence of rebleeding, but also due to the development of cerebral vasospasm and/or hydrocephalus resulting in delayed cerebral ischaemia. Indeed, it has been reported that cerebral ischaemia arises as a result of a combination of cerebral vasospasm and raised intracranial pressure, leading to a reduction in cerebral perfusion (Brinker et al. 1992).The observation that patients presenting elevated plasma renin levels experience a higher incidence of mortality and morbidity than those with lower plasma renin (NeilDwyer et al. 1980) indicates that the renin-angiotensin system may be involved in some of the deleterious consequences of SAH. Whether this occurs as a result of angiotensin II generating cerebral vasospasm remains to be seen. Interestingly, in experimental studies of SAH in rats (Honda et al. 1997) and dogs (Andrews et al. 1982), delayed cerebral vasospasm is reversed by the use of an angiotensin-converting enzyme inhibitor.The role of the central angiotensin II system in the pathology of SAH is not well known. The combined activation of both the peripheral and central angiotensin systems may play a role in the pathophysiology following SAH. Indeed, increases in both angiotensin II-like immunoreactivity and angiotensin II receptor content at the circumventricular organs, organum vasculosum lamina terminalis and subfornical organs in the rat following SAH have been demonstrated (Acikgoz et al. 1996). It is therefore feasible that antagonists of angiotensin II receptors may be of benefit in the management of patients following SAH. Contrary to this view, in some recent experiments we found that activation of the renin-angiotensin system following Impact of the renin-angiotensin system on cerebral perfusion following subarachnoid haemorrhage in the rat 1. This study investigated the effects of blocking the AT 1 angiotensin receptors with irbesartan, either peripherally or centrally, on systemic blood pressure, intracranial pressure and cerebral perfusion pressure following experimental subarachnoid haemorrhage (SAH) in urethaneanaesthetized rats. Sympathetic nervous activation was determined by measuring plasma noradrenaline levels.2. In untreated animals, SAH induced a sustained increased in intracranial pressure from 2.1 ± 0.3 to 16 ± 2 mmHg (3 h, P < 0.001). Cerebral perfusion pressure was reduced by 20 % (P < 0.001), this reduction being maintained for 3 h. Sympathetic activation was evident in the high level of plasma noradrenaline measured 3 h post-SAH (751 ± 104 vs. 405 ± 33 pg ml _1 , P < 0.05).3. Acute peripheral pretreatment with irbesartan (3 mg kg _1 , I.V.) prevented the rise in plasma noradrenaline and further aggravated the decrease in cerebral perfusion...

Common Variants of the ACE Gene and Aneurysmal Subarachnoid Hemorrhage in a Danish Population

“…Rather, functional but hitherto unknown polymorphism(s) in the candidate region of the gene are in strong linkage disequilibrium with the I/D polymorphism. 33 In experimental animals, ACE inhibitors ameliorated intracerebral vasospasms. 13 Risk of Alzheimer disease repeatedly has been found to be associated with the I allele.…”

Systemic Up-Regulation of Angiotensin II Type 1 Receptor in Cardiac Donors with Spontaneous Intracerebral Hemorrhage

“…The data of the present study suggests that the up‐regulation of AT1R in both donor hearts and donor lymphocytes indicates the presence of a generalized activation of the RAS. This concept is supported by experimental models that showed activation of both circulating and central nervous system RAS following subarachnoid hemorrhage (13,18). In conclusion, donor spontaneous intracerebral hemorrhage is associated with up‐regulation of AT1R and subsequent development of transplant coronary vasculopathy.…”

“…Both clinical and experimental investigations suggest that the activation of the renin‐angiotensin system (RAS) occurs along with increased sympathetic drive in patients with spontaneous ICH (12). Angiotensin II interacts with the sympathetic nervous system to maintain an adequate cerebral perfusion (13,14). Clinical studies have demonstrated that plasma renin activity may correlate with the size of bleed and prognosis in subjects after subarachnoid hemorrhage (15,16).…”

“…Furthermore, the blockade of AT1R may have deleterious effect on the course of subarachnoid hemorrhage (17). It seems plausible that the activation of RAS, which exerts a protective effect by counteracting the elevation in intracranial pressure that occurs following ICH, such as subarachnoid hemorrhage (13), may have a detrimental effect on the donor heart. The data of the present study suggests that the up‐regulation of AT1R in both donor hearts and donor lymphocytes indicates the presence of a generalized activation of the RAS.…”

Effects of common medications on cerebral vasospasm after subarachnoid haemorrhage

“…Some animal studies provide supporting evidence for this hypothesis [34,35], although the data are controversial [36,37]. In the authors' large, retrospective study of medication exposures and SAH-associated vasospasm, prior use of ACE inhibitors and ARBs had no effect on the incidence or severity of vasospasm and on clinical outcome [29].…”