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Hypotensive action of adrenomedullin (ADM) receptor blockade in the rostral ventrolateral medulla of spontaneously hypertensive rats
Author(s) -
Colombari Debora Simoes Almeida,
Milosavljevic Snezana,
Colombari Eduardo,
JapundzicZigon Nina,
Paton Julian F.R.,
Murphy David
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1008.9
Subject(s) - rostral ventrolateral medulla , medicine , endocrinology , adrenomedullin , receptor , mean arterial pressure , vasomotor , chemistry , medulla oblongata , blood pressure , central nervous system , heart rate
Microarray data from our laboratory indicate that mRNA levels for the ADM receptor (GRP182) are upregulated by 2.9 fold in SHR compared to Wistar‐Kyoto (WKY) rats. Further, ADM increases mean arterial pressure (MAP) when microinjected into the rostral ventrolateral medulla (RVLM) of anesthetized normotensive rats (Xu and Krukoff, 2004; AJP , 287 , p R729). We tested the hypothesis that blockade of ADM receptors in the RVLM of spontaneously hypertensive rats (SHR) would reduced arterial pressure. Animals were anesthetized with urethane (1.4 g/kg, iv) and an ADM antagonist (ADM 22‐52, 100 fmol/100 nl) was microinjected bilaterally into the RVLM. In the SHR MAP decreased by ‐42 ± 3 mmHg after ADM receptor blockade (n=6; P<0.01); this response peaked 20 min after drug delivery. Conversely, ADM 22‐52 injected either into RVLM of WKY rats (n=6) or outside the RVLM in SHR (n=5) failed to change MAP. In arterially perfused rats (n=3), ADM (100 fmol/100 nl) microinjected bilaterally into the RVLM of SHR produced a time‐dependent increase in thoracic sympathetic chain activity (34 ± 4 and 81 ±13%, at 20 and 60 min) but in stark contrast, no change in WKY rats. These results demonstrate that in SHR there is tonic endogenous activation of ADM receptors that directly excite vasomotor sympathetic activity. This may, in part, reflect the high mRNA levels in the RVLM of the SHR compared to WKY rat. Support: CNPq, CAPES (Brazil), The Royal Society.