Use of modified vasoactive intestinal peptides in the treatment of hypertension

1. A method for treating hypertension in a patient, comprising administering to the patient: a vasoactive intestinal peptide (VIP) having a binding preference for the Vasoactive Intestinal Peptide Receptor 2 (VPAC2), and at least one anti-hypertensive drug selected from a β1 receptor antagonist, an ACE inhibitor, and a calcium channel blocker, wherein the VIP comprises the amino acid sequence of SEQ ID NO: 13 with the N-terminal His at position 2, an N-terminal methionine, and an elastin-like peptide (ELP) at the C-terminus, wherein the ELP comprises at least 90 repeats of VPGXG (SEQ ID NO: 3), wherein the VIP demonstrates an extended half-life in circulation, and wherein the co-administration of the VIP and the anti-hypertensive drug produces a synergistic increase in long-lasting blood pressure control compared to administering VIP alone.

2. The method of claim 1 , wherein said hypertension is selected from pulmonary hypertension, uncontrolled essential hypertension, and resistant hypertension.

3. The method of claim 1 , wherein said vasoactive intestinal peptide induces vaso-relaxation.

4. The method of claim 1 , wherein said vasoactive intestinal peptide induces decrease of at least one of systolic pressure, diastolic pressure, and mean arterial pressure.

5. The method of claim 1 , wherein X is independently selected from V, A, and G.

6. The method of claim 5 , wherein X is V, A, and Gina ratio of about V5, A2, and G3.

7. The method of claim 1 , wherein said elastin-like peptide component comprises 120 repeating units of VPGXG (SEQ ID NO: 3).

8. The method of claim 7 , wherein said vasoactive intestinal peptide has the amino acid sequence of SEQ ID NO: 14.

9. The method of claim 1 , wherein said β1 receptor antagonist is Atenolol.

10. The method of claim 1 , wherein said ACE inhibitor is Ramipril.

11. The method of claim 1 , wherein said calcium channel blocker is Amlodipine.

12. The method of claim 1 , wherein said vasoactive intestinal peptide and said anti-hypertensive drug are administered separately.

13. The method of claim 1 , wherein said vasoactive intestinal peptide is administered parenterally.

14. The method of claim 13 , wherein said vasoactive intestinal peptide is administered subcutaneously.

15. The method of claim 1 , wherein said vasoactive intestinal peptide is administered about once per day.

16. The method of claim 1 , wherein said vasoactive intestinal peptide is administered about once per week.

17. The method of claim 1 , wherein said vasoactive intestinal peptide has the amino acid sequence of SEQ ID NO:14 and is administered at a dose of about 1 microgram to about 100 milligrams per kilogram of body weight.

18. The method of claim 17 , wherein said vasoactive intestinal peptide is administered at a dose of about 10 micrograms to about 10 milligrams per kilogram of body weight.

19. The method of claim 1 , wherein said patient is a human patient.

20. A pharmaceutical composition comprising a vasoactive intestinal peptide (VIP) having a binding preference for the Vasoactive Intestinal Peptide Receptor 2 (VPAC2), and at least one anti-hypertensive drug selected from a β1 receptor antagonist, an ACE inhibitor, and a calcium channel blocker, wherein the VIP comprises the amino acid sequence of SEQ ID NO: 13 with the N-terminal His at position 2, an N-terminal methionine, and an elastin-like peptide (ELP) at the C-terminus, wherein the ELP comprises at least 90 repeats of VPGXG (SEQ ID NO: 3), wherein the VIP demonstrates an extended half-life in circulation, and wherein the co-administration of the VIP and the anti-hypertensive drug produces a synergistic increase in long-lasting blood pressure control compared to administering VIP alone.

21. The pharmaceutical composition of claim 20 , wherein the composition is formulated for once per day dosing.

22. The pharmaceutical composition of claim 20 , wherein the composition is formulated for once per week dosing.