Method of increasing natriuretic activity by administering natriuretic polypeptides with unique pharmacologic profiles
View Patent ↗This document provides natriuretic polypeptides. For example, this document provides polypeptides having a natriuretic activity. In some cases, a polypeptide provided herein can have natriuretic activities without inducing excessive hypotension. This document also provides methods and materials for inducing natriuretic activities within a mammal.
1. A method for increasing natriuretic activity within a mammal, wherein said method comprises administering, to said mammal, a composition comprising a polypeptide under conditions wherein natriuretic activity within said mammal is increased and under conditions wherein the renal perfusion pressure of said mammal is maintained to a greater extent than the renal perfusion pressure maintained in a control mammal administered human BNP, wherein said polypeptide is less than 44 amino acid residues in length and comprises, in an order from amino terminus to carboxy terminus:
(a) the sequence set forth in SEQ ID NO:6 or the sequence set forth in SEQ ID NO:6 with no more than two additions, subtractions, or substitutions,
(b) the sequence set forth in SEQ ID NO:2 or the sequence set forth in SEQ ID NO:2 with no more than one addition, subtraction, or substitution, and
(c) the sequence set forth in SEQ ID NO:7 or the sequence set forth in SEQ ID NO:7 with no more than two additions, subtractions, or substitutions.
2. The method of claim 1 , wherein said composition comprises a pharmaceutically acceptable carrier.
3. The method of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6, the sequence set forth in SEQ ID NO:2, and the sequence set forth in SEQ ID NO:7.
4. The method of claim 1 , wherein said polypeptide is a substantially pure polypeptide.
5. The method of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6.
6. The method of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6 with no more than two additions, subtractions, or substitutions.
7. The method of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6 with one addition, subtraction, or substitution.
8. The method of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:2.
9. The method of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:2 with one addition, subtraction, or substitution.
10. The method of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:7.
11. The method of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:7 with no more than two additions, subtractions, or substitutions.
12. The method of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:7 with one addition, subtraction, or substitution.
13. The method of claim 1 , wherein said polypeptide, when administered to a mammal, induces a decrease in mean arterial pressure to a lesser extent than that induced by human BNP, when said human BNP is administered to a mammal.