Probiotics may Emerge as Novel Drug Delivery Systems in Pulmonary Hypertension

Highlights

• A high blood pressure in the lung circulation is called pulmonary hypertension. It can have adverse consequences on the heart.
• A peptide called Angiotensin-(1-7) has beneficial effects in pulmonary hypertension, but cannot be given orally since it gets destroyed in the digestive tract.
• Researchers are exploring the possible use of the probiotic bacterium lactobacillus to deliver the peptide to the lungs.

In a study presented at the American Heart Association's Council on Hypertension 2016 at Orlando, Florida, researchers have demonstrated reduced pulmonary blood pressure in rats with experimentally-induced pulmonary hypertension who were orally administered a genetically-modified probiotic bacterium, Lactobacillus paracasei. Pulmonary hypertension is a condition where the blood pressure in the lung circulation increases. Since blood from the right side of the heart enters the pulmonary circulation via the pulmonary artery to get oxygenated, the heart has to pump against the increased pressure. The heart muscle therefore thickens to maintain the contraction. The patient may eventually suffer from right-sided heart failure.

Drugs belonging to the calcium channel blocker group, prostacyclin analogues like epoprostenol and treprostinil, endothelin receptor antagonists like ambrisentan and bosentan, and phosphodiesterase – 5 inhibitors like tadalafil have been used in the treatment of pulmonary hypertension. Treatment with oxygen and lung transplantation may be required in severe cases.

A peptide called Angiotensin -(1-7) or Ang-(1-7) is known to have beneficial effects in pulmonary hypertension. However, the peptide gets destroyed in the digestive tract when taken orally. Researchers have devised a way to prevent its degradation in the digestive tract. They have genetically modified the probiotic bacterium Lactobacillus paracasei to produce and secrete Ang-(1-7). The researchers tested their invention in rats with pulmonary hypertension, in whom the disease was brought about by the injection of a chemical called monocrotaline.

The rats with pulmonary hypertension were administered the genetically modified lactobacillus orally. The researchers found that compared to untreated rats with experimentally induced pulmonary hypertension, the treated rats had:

• A 43% reduction in blood pressure on the right side of the heart. An elevated blood pressure on the right side of the heart is indicative of pulmonary hypertension
• A 33% reduction in the thickness of heart wall and an improvement in the contractility of the heart wall. Thus, there is an improvement in the cardiac consequences of pulmonary hypertension.

Thus, there is a possibility that modified lactobacillus may be useful in the treatment of pulmonary hypertension and its associated complications on the heart in the future either alone or in combination with other medications.

Reference:

1. Jeffery CC et al. Genetically Modified Probiotics for Oral Delivery of Angiotensin-(1-7) Confers Protection Against Pulmonary Hypertension. American Heart Association's Council on Hypertension 2016 Scientific Sessions.

Source-Medindia