Supowit S C, Zhao H, Wang D H, DiPette D J
Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA.
Hypertension. 2001 Sep;38(3 Pt 2):697-700. doi: 10.1161/hy09t1.095759.
Calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide, plays a counterregulatory role in subtotal nephrectomy-salt (SN-salt)-induced hypertension, reflecting a stimulation of the efferent vasodilator function of perivascular sensory nerves. To determine the effect of omapatrilat, a dual ACE and neutral endopeptidase inhibitor, on blood pressure and the potential antihypertensive role for CGRP, 24 male Sprague-Dawley rats were separated into 4 groups: (1) SN-salt, (2) SN-salt plus omapatrilat (80 mg. kg(-1). d(-1) in the drinking water), (3) sham-operated plus salt, (4) sham-operated plus salt and omapatrilat. After 11 days the mean arterial pressure was higher in the SN-salt group (174+/-10 mm Hg) versus the sham-operated-salt (109+/-4 mm Hg) and sham-operated-salt plus omapatrilat (105+/-3 mm Hg) groups. Omapatrilat treatment of the SN-salt rats significantly decreased the mean arterial pressure to 123+/-7 mm Hg and significantly reduced the heart-to-body weight ratio. Intravenous administration of a specific CGRP receptor antagonist produced a significant 10+/-2 mm Hg mean arterial pressure increase in the untreated SN-salt hypertensive rats but was without effect in the other groups. This indicates that CGRP does not contribute to the antihypertensive actions of omapatrilat. In addition, CGRP mRNA and protein content in dorsal root ganglia were decreased approximately 25% in the SN-salt plus omapatrilat rats. Thus, omapatrilat not only markedly reduces the blood pressure in this model of renal failure-induced hypertension but may also prevent the abnormal compensatory stimulation of the vasodilator activity of the peripheral sensory nervous system.
降钙素基因相关肽（CGRP）是一种强效血管舒张神经肽，在肾次全切除-盐（SN-盐）诱导的高血压中发挥反调节作用，这反映了对血管周围感觉神经传出血管舒张功能的刺激。为了确定双重ACE和中性内肽酶抑制剂奥美帕替拉对血压的影响以及CGRP潜在的降压作用，将24只雄性Sprague-Dawley大鼠分为4组：（1）SN-盐组，（2）SN-盐加奥美帕替拉组（饮用水中80 mg·kg⁻¹·d⁻¹），（3）假手术加盐水组，（4）假手术加盐水和奥美帕替拉组。11天后，SN-盐组的平均动脉压（174±10 mmHg）高于假手术-盐水组（109±4 mmHg）和假手术-盐水加奥美帕替拉组（105±3 mmHg）。对SN-盐大鼠进行奥美帕替拉治疗可使平均动脉压显著降至123±7 mmHg，并显著降低心重与体重比。静脉注射特异性CGRP受体拮抗剂可使未治疗的SN-盐高血压大鼠平均动脉压显著升高10±2 mmHg，但对其他组无影响。这表明CGRP对奥美帕替拉的降压作用无贡献。此外，SN-盐加奥美帕替拉大鼠背根神经节中的CGRP mRNA和蛋白含量降低了约25%。因此，奥美帕替拉不仅能显著降低这种肾衰竭诱导的高血压模型中的血压，还可能预防外周感觉神经系统血管舒张活性的异常代偿性刺激。
