ArticleStructural Requirements and Mechanism of the Pressor Activity of Leu-Val-Val-hemorphin-7, a Fragment of Hemoglobin β-chain in Rats
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The Rat Blood Pressure Assay
All experiments were performed using male Sprague-Dawley rats (400–500 g) purchased from Charles River Canada Inc., St-Constant, Québec, Canada. The animals were housed 2–3 per cage, given rat purina chow and tap water ad libitum, and kept under stable environmental conditions for a few days before use. Experiments were conducted in accordance with the principles and guidelines of the Canadian Council on Animal Care and approved by the local Institutional Committee on Animal Care.
The animals
Pressor Activity of LVV-H7, Its Fragments and Analogs
IV injections of 38, 76, 152 and 228 nmoles/kg of LVV-H7 in anesthetized, vagotomized rats elicited pressor effects (ΔMABP: 9 ± 2, 17 ± 2, 36 ± 3 and 37 ± 2 mmHg, respectively) and tachycardia (▵HR: 2 ± 1, 10 ± 2, 21 ± 3 and 25 ± 3 beat/min, respectively) (n = 45). Peak BP and HR responses to 152 nmoles/kg of LVV-H7 occurred at 14 ± 2 sec (n = 13) and 20 ± 2 sec (n = 11) after injection, respectively. Both the pressor effect and tachycardia elicited by LVV-H7 (152 nmoles/kg) were short-lasting
Structure–Pressor Activity Relationships of LVV-H7
Studies with Ala-containing derivatives of LVV-H7 were quite informative, despite the fact that replacement of the normal constituents of LVV-H7 with Ala gives equal weight to all positions in the peptide chain, without considering their presumably unequal importance for the pressor activity of LVV-H7 as a whole. Replacement of Phe7, Arg6 or Trp3 by Ala abolished partially (LVV-[Ala3]H7) or completely (LVV-[Ala7]H7 and LVV-[Ala6]H7) the pressor activity of LVV-H7, whereas replacement of all
Acknowledgements
The authors wish to thank Mrs. Elisabeth Lemay for typing this manuscript, and Baxter Healthcare Corporation for their financial support (contract no. 2A-S-0153).
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