Methods of treating hypertension and compositions for use therein

DETAILED DESCRIPTION The present invention provides methods of treating hypertension, particularly essential hypertension.
The methods generally involve providing a stimulator of angiogenesis and/or of blood vessel porosity to maintain or correct the transport of solutes, including sodium chloride, and fluid across a basement membrane separating blood vessels or other vessels containing endothelium from epithelial cells.
Such transport can be from the blood vessel across the basement membrane to or by the epithelial cells; or it can be from or by epithelia across the basement membrane to blood vessels.
Stimulation of vessel number or porosity is used to increase the efficiency or extent of solute transport, thus decreasing blood volume and the concomitant hypertension.
In one aspect, the invention concerns a method for treating essential hypertension, comprising administering to a patient an effective amount of an angiogenic factor, or an agonist thereof.
The angiogenic factor can be administered alone or in combination with a further anti-hypertensive agent, such as another angiogenic factor, and preferably is a vascular endothelial growth factor (VEGF) molecule.
The vascular endothelial growth factor is preferably selected from the group consisting of native hVEGF145 (FIG.
7, SEQ ID NO: 2), native hVEGF165 (FIG.
8, SEQ ID NO: 3), native hVEGF189 (FIG.
9, SEQ ID NO: 4), native hVEGF206 (FIG.
10, SEQ ID NO: 5), and agonists of any one of such native VEGF proteins.
In a particularly preferred embodiment, the VEGF molecule lacks the ability to bind heparin, and is, for example, hVEGF121.
The hypertension preferably is salt-dependent hypertension.
In another aspect, the invention concerns an article of manufacture comprising: a container; a composition comprising an angiogenic factor or an agonist thereof, in an amount effective in the treatment of hypertension; and instructions to administer the composition for the treatment of hypertension.
Again, the composition may contain an additional anti-hypertensive agent, e