title: Exogenous ghrelin improves blood flow distribution in pulmonary hypertension-assessed using synchrotron radiation microangiography.
abstract: Ghrelin has cardioprotective properties and, recently, has been shown to improve endothelial function and reduce endothelin-1 (ET-1)-mediated vasoconstriction in peripheral vascular disease. Recently, we reported that ghrelin attenuates pulmonary hypertension (PH) caused by chronic hypoxia (CH), which we hypothesized in this study may be via suppression of the ET-1 pathway. We also aimed to determine whether ghrelin's ability to prevent alterations of the ET-1 pathway also prevented adverse changes in pulmonary blood flow distribution associated with PH. Sprague-Dawley rats were exposed to CH (10% O(2) for 2 weeks) with daily subcutaneous injections of ghrelin (150 μg/kg) or saline. Utilizing synchrotron radiation microangiography, we assessed pulmonary vessel branching structure, which is indicative of blood flow distribution, and dynamic changes in vascular responsiveness to (1) ET-1 (1 nmol/kg), (2) the ET-1(A) receptor antagonist, BQ-123 (1 mg/kg), and (3) ACh (3.0 μg kg⁻¹ min⁻¹). CH impaired blood flow distribution throughout the lung. However, this vessel "rarefaction" was attenuated in ghrelin-treated CH-rats. Moreover, ghrelin (1) reduced the magnitude of endothelial dysfunction, (2) prevented an increase in ET-1-mediated vasoconstriction, and (3) reduced pulmonary vascular remodeling and right ventricular hypertrophy-all adverse consequences associated with CH. These results highlight the beneficial effects of ghrelin for maintaining optimal lung perfusion in the face of a hypoxic insult. Further research is now required to establish whether ghrelin is also an effective therapy for restoring normal pulmonary hemodynamics in patients that already have established PH.
authors: Department of Physiology, University of Otago, Dunedin, New Zealand. daryl.schwenke@otago.ac.nz
authors: Daryl O
authors: DO
authors: Schwenke
authors: Emily A
authors: EA
authors: Gray
authors: James T
authors: JT
authors: Pearson
authors: Takashi
authors: T
authors: Sonobe
authors: Hatsue
authors: H
authors: Ishibashi-Ueda
authors: Isabel
authors: I
authors: Campillo
authors: Kenji
authors: K
authors: Kangawa
authors: Keiji
authors: K
authors: Umetani
authors: Mikiyasu
authors: M
authors: Shirai
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000792:Angiography / Q000379:methods*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D054439:Ghrelin / Q000494:pharmacology* / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008168:Lung / Q000098:blood supply*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects*; D017356:Synchrotrons; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D019332:Endothelin-1; D054439:Ghrelin; D010456:Peptides, Cyclic; D014665:Vasodilator Agents; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)