High blood pressure, or hypertension, affects about 320 million Indians. Untreated, the condition could lead to cardiovascular complications, trigger kidney issues and cause eye trouble.
Recent research by Prof Nitish Mahapatra and his team at IIT-Madras has shown how a peptide and its variant have vastly different effects in the natural control of hypertension.
A peptide is a short chain of amino acids that serves as a building block for proteins. Catestatin is a peptide made up of 21 amino acids. The study focused on how the normal form of catestatin (called wild type, or CST-WT) and a common variant (Gly364Ser, CST-Serine) affect cardiovascular function.
But what made the researchers focus on these peptides in particular?
Says Prof Mahapatra, “We narrowed down on them because we had published a paper in 2016, in a journal called Hypertension, where we showed that people harbouring the variant peptide were more prone to developing hypertension.”
The study had analysed about 4,000 people across India and found that 15 per cent carried the serine variant. Their risk of developing hypertension was about twofold greater that those with the wild-type.
Their latest paper is the culmination of the 2016 study. “In the animal model, we saw that what we had hypothesised was indeed correct,” he says. “We found the wild-type form of the peptide to be antihypertensive in our laboratory.”
Heart function test
Hypertension, or high blood pressure, is a condition where the force of blood against the walls of blood vessels remains high over time.
In the IIT-Madras study, rats were fed a high-salt diet for a few months. The animals, which had become hypertensive, were injected with the normal or wild-type peptide. It was observed that their blood pressure dropped to normal within two hours, and the effect usually lasts 24 hours or so. On the other hand, when the serine variant was injected the blood pressure remained high.
The study also measured heart rate and observed the electrical activity of the heart using an electrocardiogram. High heart rates are known to be associated with heart diseases.
The wild-type form of the peptide was able to reduce the heart rate in hypertensive rats, whereas the serine variant showed a smaller effect. In addition, improvement in heart muscle contractions, which reflect how strongly the heart pumps blood, was greater with the wild-type peptide than with the serine variant.
Measurements of pressure in the heart both during contraction and relaxation showed that the CST-WT peptide helped restore normal heart function better than the variant.
The heart tissue from hypertensive rats also showed evidence of inflammation and cell damage. Rats treated with the wild-type peptide had less tissue damage and fewer signs of inflammation than those treated with the serine variant.
One step ahead
So, are the researchers working with pharmaceutical firms to formulate a drug that addresses high blood pressure?
“Right now, we are doing something different,” Mahapatra says.
After its latest research was published, the team is modifying amino acids of the wild-type peptide to make it even more potent and stable. The study focused on naturally occuring peptides — both wild-type and serine, Mahapatra explains.
The effort now is to modify them to help keep blood pressure under control for a longer period of time.
Eventually, that part of the team’s work would go for human clinical trials in collaboration with pharmaceutical companies.
