Horm Metab Res 2010; 42(11): 803-808
DOI: 10.1055/s-0030-1262782
Animals, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Prevention of Hypertensive Crises in Rats Induced by Acute and Chronic Norepinephrine Excess

D. Weismann1 , K. Kleinbrahm1 , K. Hu1 , M. Fassnacht1 , S. Frantz1 , G. Ertl1 , B. Allolio1 , S. K. G. Maier1
  • 1Department of Internal Medicine I, University of Würzburg, Würzburg, Germany
Further Information

Publication History

Publication Date:
27 July 2010 (online)

Abstract

Calcium Channel Blockers (CCBs), competitive α-adrenoceptor blockers, and phenoxybenzamine (POB) are used for preoperative treatment of pheochromocytomas. We analyzed the protection from hypertensive crisis provided by these drugs during acute and chronic norepinephrine excess. To ensure adaptive changes during chronic norepinephrine (NE) excess, we continuously exposed male Wistar rats to NE for 3 weeks (osmotic pumps). Afterwards, blood pressure (BP) was continuously measured while NE boli (0–1 000 μg/kg, i. v.) were administered before and after antihypertensive treatment in anesthetized and catheterized rats. A single dose of urapidil (10 mg/kg), nitrendipine (600 μg/kg) and POB (10 mg/kg) lowered BP from 212±12 mmHg by 52±7%, 31±9%, and 50±6%, respectively. With NE boli a maximum BP of 235±29, 240±30 and 138±3 mmHg was measured in urapidil, nitrendipine, and POB treated animals (p<0.05). The number of hypertensive episodes (delta BP >30 mmHg) was 3 (3), 1.5 (0–3), and 0 (0–1) (p<0.05). Because of inferiority, urapidil was excluded from further testing. Chronically NE exposed rats were treated with POB (10 mg/kg/d), nifedipine (10 mg/kg/d), or vehicle for 7 days. Marked BP elevations were observed at baseline (167±7, 210±7, and 217±7 mmHg, p<0.01) and maximum blood pressure was 220±32, 282±26, and 268±40 mmHg (p<0.001) with NE boli. Further stabilization was achieved combining POB pretreatment with a continuous nifedipine infusion, which effectively prevented BP elevations during NE excess. POB was the most effective drug used in monotherapy, but BP stabilization was superior using a combination of POB pretreatment with a continuous nifedipine infusion in this model.

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Correspondence

Dr. S. K. G. Maier

Medizinische Klinik und

Poliklinik I

Universitätsklinikum Würzburg

Oberdürrbacher Straße 6

97080 Würzburg

Germany

Phone: +49/931/201 43540

Fax: +49/931/201 643550

Email: maier_s@klinik.uni-wuerzburg.de