"If you filter more, you have more salt available for excretion," Inscho said. He wants to know what's happening with A and B receptors inside the tiny vasculature of the kidneys. He's using B-deficient rats and drugs that block either receptor to get a better idea about both. The idea is to figure out not just how they normally work but how the system becomes dysfunctional in hypertension. "I think we are beginning to understand how the B receptor may factor into some other regulatory systems the kidney may use to control filtration," he said.

Noted Jennifer Pollock, "Your kidneys in theory should be able to lower your blood pressure but because people do remain hypertensive, that means there must a problem with your kidneys as well." She suspects that endothelin activates production of nitric oxide when it hits the B receptor. Nitric oxide, which dilates blood vessels, prompts the sodium channels in kidney tubules to fold inward.

"The salt can't get in and so it gets excreted," Jennifer Pollock said. "We are connecting the dots now." If they are correct, they have found a new mechanism for controlling salt excretion that is a natural drug target. Since it's difficult to enhance nitric oxide, it likely will be necessary to find another cue to prompt sodium channels to fold up their tents. She developed a mouse lacking nitric oxide synthase, which prompts nitric oxide production, to help pursue the theory.

Co-investigator Dr. James Stockand in Texas is investigating mechanisms for how endothelin affects transport of sodium in and out of the cell, focusing on proteins known as ion channels. Dr. Jennifer Sullivan, pharmacologist/physiologist at MCG's Vascular Biology Center, is providing support and expertise with the numerous animal models needed for the grant.

"The future of pharmaceutical therapies is going to be the right balance of different drugs," said David Pollock. "Most people with high blood pressure are also taking cholesterol medicine and possibly other drugs. So the future has to be what is the right formula for you and your situation."

The scientists hope their studies will point the way to these new, targeted options.

Source: Medical College of Georgia