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Hemin therapy suppresses established hypertension in adult hypertensive rats
Author(s) -
Lane Nina,
Pande Vivek,
Ndisang Joseph Fomusi
Publication year - 2007
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.21.6.a798-b
Subject(s) - hemin , heme oxygenase , heme , blood pressure , antioxidant , medicine , endocrinology , biliverdin , chemistry , inducer , bilirubin , pharmacology , nitric oxide , biochemistry , enzyme , gene
Acutely applied heme oxygenase inducers lowers blood pressure (BP) of young spontaneously hypertensive rats (SHR) but not adult with established hypertension. Heme oxygenase breaks down heme to produce carbon monoxide, biliverdin/bilirubin with antioxidant/anti‐inflammatory actions while the iron formed induces the formation of ferritin, an antioxidant. In the present study, the heme oxygenase inducer, hemin, was administered at a dose of 15 mg/kg to two groups of adult (20 weeks) SHR by subcutaneous (s.c.) and intraperitoneal (i.p.) routes respectively for 23 days. Hemin given i.p. and s.c. routes effectively reduced blood pressure to physiological levels in adult SHR from 202.4±2.4 to 138.6±2.2 mmHg (p< 0.01, n=8) and from 202.2±1.2 to 125.7±1.1 mmHg (p<0.01, n=6) respectively. The i.p. route was more effective in reducing BP. Hemin given by i.p reduced BP by 76 mmHg whereas by s.c. the reduction was 63 mmHg. Hemin given by s.c. or i.p. route did not affect blood pressure in normotensive age‐matched Sprague Dawley (SD) rats (120.5±1.6 vs. 124.3±1.5 mmHg, n=6) and (123.5±1.6 vs. 123.6±1.7 mmHg, n=5) respectively. The antihypertensive effect of hemin was accompanied by increased levels of carbon monoxide signalling agents (HO‐1, HO activity, cGMP, and PKG), all of which enhance vascular relaxation. Contrarily, hemin therapy abrogated PLC and IP 3 activities. Thus, the potentiation of vasorelaxant mechanisms, accompanied by the concomitant suppression of vasoconstrictor pathways may account for the antihypertensive effects of hemin. (This work is supported by Heart & Stroke Foundation of Saskatchewan, Canada)