Increased angiotensin type 1A receptor activity in the rostral ventrolateral medulla of normotensive rats induces a transient increase in blood pressure

University of Bristol (2005) J Physiol 567P, C36

Oral Communications: Increased angiotensin type 1A receptor activity in the rostral ventrolateral medulla of normotensive rats induces a transient increase in blood pressure

Allen, Andrew Mark; Dassanayake, Sasha; Dosanjh, Jaspreet; Hannan, Ross D; Thomas, Walter G;

1. Physiology, University of Melbourne, Parkville, VIC, Australia. 2. Baker Heart Research Institute, Melbourne, VIC, Australia.

View other abstracts by:


Neurons located in the rostral ventrolateral medulla (RVLM) are essential for the tonic and reflex regulation of sympathetic vasomotor activity (1). These neurons are excited by angiotensin II acting through AT1 receptors (2). In spontaneously hypertensive rats, but not in normotensive Wistar Kyoto (WKY) rats, activation of AT1 receptors in RVLM contributes to the observed hypertension (3). The current experiments aimed to determine whether increased AT1 receptor density or activity in the RVLM of WKY rats could chronically increase blood pressure. All experiments were performed in accordance with the Australian NH&MRC code of conduct and were approved by the Institutional Animal Experimentation Committees. Metacam (1 mg/kg) was administered subcutaneously 1 h before each surgery as an analgesic. Under equithesin anesthesia (0.3 ml/100g), male WKY rats (240-280g) were implanted with blood pressure telemeters (DSI). Following 7-10 days recovery blood pressure was recorded daily (between 3 and 4 p.m.) for 7 days. On the 8th day bilateral microinjections of replication-deficient adenoviruses (4 x 100 nl of 1×107 PFU/μl) were made into the RVLM under isoflurane anesthesia (1.8-2.4% in room air). Two viral constructs were used inducing expression, under the control of the cytomegalovirus promoter, of green fluorescent protein (GFP) and either a wild-type AT1a receptor or a constitutively active AT1 receptor mutant (N111G). Blood pressure was recorded for another 7 days. The rats were then deeply anesthetized, perfused with 4% paraformaldehyde and brains processed for localization of GFP. The results describe experiments where adenovirus-induced expression of GFP was confined to the RVLM bilaterally. Increased AT1 receptor activity (N111G) increased mean arterial blood pressure for 4 days before it returned to control levels (n=5, control, 99±0.3 mmHg; 3 days post injection, 113±3 mmHg). Increased expression of the wild-type AT1 receptor (n=5) did not affect blood pressure. We demonstrate that increased AT1 receptor activity in the RVLM induces a transient increase in blood pressure. Transgene expression, under the control of the CMV promoter, occurs in astrocytes in the RVLM (4) indicating that local changes in astrocytic function may lead to changes in the activity of RVLM premotor neurons.



Where applicable, experiments conform with Society ethical requirements.

Site search

Filter

Content Type