Gene Therapy Eliminates High Blood Pressure in Rats and Offspring
Nov. 12, 1999 (Atlanta) -- Researchers have used gene therapy to essentially cure high blood pressure, also called hypertension, in rats and their offspring, according to a study published in the Nov. 12 issue of Research Circulation: Journal of the American Heart Association.
The researchers used an inactive virus to introduce the new gene into newborn rats (specially bred to develop high blood pressure) and found that it prevented the development of hypertension for life. "And when you breed these rats ... the antihypertensive effect is transmitted to at least two generations of offspring," senior author Mohan Raizada, PhD, tells WebMD. "The reason we feel it's important is, this is the first time a therapeutic gene is being introduced and its effect, or its consequence, is expressed in the offspring." Raizada is a professor of physiology at the University of Florida College of Medicine in Gainesville.
The researchers decided to try to attack a system in the body that is vital in the control of blood pressure, known as the renin-angiotensin system. Blocking this system with medications leads to a significant improvement in hypertension. Medications that act on this system are called ACE inhibitors and include such drugs as Vasotec (enalapril maleate), Prinivil (lisinopril), and Altace (ramipril), and many others. In addition, a newer class of medications called angiotensin receptor blockers, including Cozaar (losartanpotassium) and Diovan (valsartan), also block this system but in a slightly different way.
"So we thought if we are going to try to test gene therapy, we should use the same approach [as the drugs]. So what we did is we tried to inhibit the expression of the renin-angiotensin system ... at the genetic level," says Raizada.
"When we found [no hypertension] even when the [rats] were 200 days old, which is almost like old age for the rats, we decided to extend the experiment and see if it [was present] in the offspring. This is really kind of an offshoot of the [original] study," says Raizada.
To test their hypothesis, the researchers, led by Phyllis Reaves, PhD, divided regular rats and the specially bred rats into two groups: half of each group received a shot of gene therapy; the other half received a shot of an inactive chemical. At 100 days, two sets of parents from each of the four groups were bred to generate offspring; the offspring were similarly bred to generate the next generation of offspring. The animals all had their blood pressure monitored at various times during the study. In both generations, offspring of the gene therapy rats had significantly lower blood pressure compared with the offspring from the other rats. Raizada says he's not sure why or how the effect of this particular gene therapy appears to be passed on to future generations.