Blogged from sciencexplained.blogspot.com

Thickening of the heart muscle wall, hypertrophy, in response to high blood pressure can lead to enlargement of the heart and often heart failure and death. A study in the Feb issue of the journal Nature Medicine shows that blood pressure-induced hypertrophy can be prevented or reversed in mice treated with the drug sildenafil, better known as Viagra. The study offers promise for the treatment of hypertrophy in humans and provides a much sought after source of bad puns.

During extended periods of high blood pressure, for instance in non-managed chronic hypertension, the heart responds by thickening its muscular wall to try and compensate for the increased pressure load. This thickening is termed hypertrophy. In the short term this may be a useful adaptive response, but in the long term it can have very deleterious effects. In particular, the resulting enlargement of the heart often leads to heart failure and eventually death. Naturally, therefore, there is much interest in finding drugs which can prevent hypertrophy and heart enlargement.

Mechanisms of Hypertrophy.
Heart cells respond to increased pressure load by growing larger, the net result being an increase in size of all or parts of the heart. The signals instructing heart cells to undergo hypertrophy are partly mechanical, i.e. the pressure increase itself, and partly from hormones which are released in response to the pressure load.
The chemical cyclic GMP, or cGMP, is what is known as a second messenger; it is produced inside cells in response to a signal from outside the cell, such as a hormone (the first messenger). When heart cells are confronted by the hormone atrial natriuretic peptide (ANP), cGMP levels in the cells increase and a chain of molecular events is set in motion, instructing the cell not to undergo hypertrophy. Therefore raising cGMP in heart cells could be a potentially useful way to counteract hypertrophy in response to increased blood pressure. There are two ways this could potentially be achieved; by increasing cGMP production or decreasing cGMP destruction. The latter process is mediated by a group of proteins called cGMP phosphodiesterases (PDEs), and it turns out there is already a class of drugs available which increase cGMP levels by blocking PDEs.

The Viagra Connection.
Sildenafil, sold as a prescription drug by Pfizer under the brand name Viagra, was the first of the new wave of drugs for erectile dysfunction (ED). Ironically, it started out as a test drug for hypertension. As in heart cells, ANP also raises cGMP levels in the smooth muscle cells which line blood vessels and this causes relaxation and dilation of the blood vessels. Pfizer researchers therefore reasoned that a drug that blocked PDEs would potentiate this cGMP elevation and could therefore be effective in treating high blood pressure. Having found an effective PDE blocker, called sildenafil, they went into clinical trials. It turned out, though, that sildenafil wasn't effective in the trials for treating hypertension, or in follow up trials for angina. However, several men in the high dose Phase I trials reported a curious and not necessarily unwelcome side effect, a bonus if you like. Although the side effect was unforeseen, in hindsight it was not surprising. Sildenafil potentiates cGMP elevation in smooth muscle cells in the penis in response to the locally acting gaseous "hormone" nitric oxide. This increases blood flow, which enables and sustains erection. Soon trials were started for ED, the drug was named Viagra, Bob Dole got on board the publicity wagon and the rest, as they say, is history.
Given the role of cGMP in preventing cardiac hypertrophy, and the ability of sildenafil to increase cGMP levels, Takimoto, Champion, Li and their colleagues at Johns Hopkins reasoned that sildenafil might correct hypertrophy caused by increased pressure load. To test the hypothesis, they performed a surgical procedure on mice called TAC, which increases cardiac pressure load, then gave them sildenafil or a placebo. The hearts of the TAC, placebo-treated mice became enlarged and their heart cells showed signs of hypertrophy. However, the heart enlargement and hypertrophy were largely prevented in the sildenafil treated mice. Interestingly, preventing hypertrophy resulted in improved cardiac performance in the sildenafil treated mice. This suggests that hypertrophy is not a necessary adaptive response, and increases confidence that anti-hypertrophic drugs will be effective in improving heart function. Heart enlargement in TAC mice was even reversed by sildenafil, causing shrinkage back to normal size, curiously the opposite of its better known action.
Heart cell hypertrophy is the result of switching on or off certain sets of genes, causing changes in the levels of key heart cell proteins involved in the development of hypertrophy. The increase in cGMP levels by sildenafil initiates a chain of molecular events leading to a block in this hypertrophic gene expression change. Understanding the precise molecular components of the response to sildenafil will be important for designing other anti-hypertrophic drugs. The current study already identifies one protein "target" of cGMP, called PGK, as playing a key role in sildenafil action. This will help scientists to see the "wood for the trees" and sets an important starting point for future studies.

Implications for Cardiovascular Therapy.
It remains to be seen whether the mouse studies will serve as a good model for human therapy, but Viagra and similar drugs are well tolerated and have a good safety record when used as prescribed, at least in men (unless you count "erections lasting longer than four hours, though rare, require immediate medical attention". Yikes!). So it should be straightforward to test these drugs on cardiac complications resulting from hypertension in men (it shouldn't be too difficult to attract volunteers for trials). It may be necessary to conduct more tests in women, to confirm that there are no additional side effects of the drugs in women.
Soon after Viagra was released as an ED drug, a number of "me too" drugs like Levitra and Cialis were made available. If PDE blockers do indeed show promise as anti-hypertrophic drugs, we can expect other drug companies to be hard on the trail, creating some stiff competition. Perhaps the initial hope that this class of drugs will be effective in treating a life-threatening cardiovascular disease might finally be realized.

Thanks to Steve - a man of Kernow.

Women have problems with their bits that cause terrible worry - and men too!
To a man to be impotent is so damaging , mentally that they feel demeaned and suicidal.
As the good doc. says above - don't worry stay happy medicene has a cure - so does nature, at a quarter of the cost, 70 percent cocoa chocolate and a big swig of cod liver oil.

I Thanky Tour
Tgordy the Tlaird