Lisinopril – for blood pressure

Hello, my friend,

In South America, there is a venomous pit viper called jararaca. Medicine from a snake? Absolutely!

In 1970, experiments were published about a peptide (a small protein) called bradykinin potentiating factor (BPF) derived in Brazil from the venom of the snake Bothrops jararaca (that’s the scientific name). BPF inhibits an enzyme found in our body called angiotensin converting enzyme (ACE). When ACE is inhibited, there is a reduction in blood pressure.

In the mid-1970s, a drug called captopril was synthesized from BPF. That was the first medication for high blood pressure in the class ACE inhibitors.

What is blood pressure (BP)? Why is it important? BP is the force that’s created against the walls of arteries as blood is transported through the body. Too much pressure can damage the arterial walls. When you take BP, it appears as two numbers. The higher number is the systolic pressure, which is the measure of the pressure when the heart pumps blood into the arteries. The lower number is the diastolic pressure, the pressure when the heart rests between beats. For an adult, the normal blood pressure is 120/80 or less. With an excited emotional state or activity, BP does rise temporarily, but it comes back to resting state.

When the BP stays consistently high, the condition is called hypertension. Over a period of time, that can lead to heart problems, kidney problems, damage of the retina in the eye, or stroke. As BP increases slowly with time, we don’t feel any symptoms. The first symptom could be death. This is why hypertension has been called the silent killer. Routine visits to the doctor now become even more important, don’t they? Catch it early, and control it.

Essential hypertension is when there appears to be no root cause – however, there are risk factors – men  are more likely to have it than women, and blacks more than whites in America. More salt in the diet, not enough potassium, calcium or magnesium in the diet, stress, obesity, diabetes, chronic uncontrolled alcohol intake, and lack of physical activity are all risk factors.

Secondary hypertension is when it is because of another condition, often kidney disease.

One of the primary mechanisms by which our body controls blood pressure is a physiological process called the renin angiotensin system. How does that work?

Certain kidney cells produce and store an enzyme called renin. This enzyme is released when there is a fall in blood pressure, or reduced sodium levels in the blood, when we are faced with a fight-flight-fright situation that activates our sympathetic nervous system, or the kidney is exposed to hormone-like substances called prostaglandins or medicinal drugs called beta-agonists.

Renin acts on a substance produced by the liver, called angiotensinogen, which circulates in the blood. The product is a peptide called angiotensin I. An enzyme called angiotensin converting enzyme (ACE) cleaves angiotensin I to produce the peptide hormone angiotensin II. Most of this last reaction happens in the capillaries of our lungs.

Angiotensin II (AII) is a very powerful agent to increase blood pressure. It does so by constricting blood vessels, and by activating the adrenal gland to release aldosterone. Aldosterone causes the kidney to reabsorb more sodium and water as a result of which there is increase in the volume of blood. This causes an increase in blood pressure. AII increases BP by a couple more mechanisms. It causes the medulla to increase cardiac output, and stimulates the hypothalamus to increase our thirst and to stimulate antidiuretic hormone (ADH) which gets the kidney to reabsorb even more water. As a result of these two mechanisms, our blood volume increases even more, causing an increase in BP.

It stands to reason that by controlling the effects of angiotensin II, we can decrease blood pressure, doesn’t it? What if we were to inhibit the enzyme that catalyzes the conversion of angiotensin I to angiotensin II? That would result in less production of AII.

That’s exactly what an ACE inhibitor does. An ACE inhibitor is a competitive inhibitor of ACE. Being structurally similar to angiotensin I, the ACE inhibitor links to ACE molecules, not leaving enough ACE to act on Angiotensin I. This means less Angiotensin II is formed.

As we saw earlier, captopril was the first in this class of anti-hypertensive drugs. The second drug was enalapril. The third, that was introduced in the early 1990s, was lisinopril (brand names in the U.S. are Prinivil and Zestril).

Lisinopril is different from other ACE inhibitors in that it does not have to be converted by the liver into another entity to activate it. It is water-soluble, penetrates body tissue very well, stays in the body for a long time (as a result, it can be given as a once-daily dose) and is excreted unchanged in the urine. Lisinopril can be used with other medicine to treat congestive heart disease or to improve survival in patients after a heart attack.

This medicine may cause dizziness or even fainting when you first start using it. Make sure you don’t drive or use any heavy machinery before you know how your body reacts to this medicine. Inform your doctor immediately if you have difficulty breathing, tightness in the chest, or swelling of face or lips, or rash/hives. Also tell your doctor immediately if you have unusual heartbeat, nausea or diarrhea, change in amount of urine, unusual joint pain or muscle pain. Drink plenty of water if engaging in activities that cause perspiration. Rarely, it can lower your resistance to infection – avoid close contact with people who have colds or other infections. If you take anti-diabetic medications, lisinopril may affect your blood sugar – please do monitor your blood sugar carefully. This drug should not be used by pregnant women. It’s unknown if it’s secreted in breast milk. It’s better not to take it while breast-feeding.

Cough is a fairly common side-effect with lisinopril and other ACE inhibitors. If it gets bothersome, tell your doctor.

Control of high blood pressure is very important to prevent heart, brain, eye, kidney and other problems as we grow older. When there is a slight consistent increase in blood pressure, your doctor will probably ask you to enforce lifestyle changes – like getting regular exercise, dietary changes like more plant-based food, less sodium, enough potassium (typically at least 3,500 mg. per day) less fat, reduction in calorie intake, controlling cholesterol through diet and medication, and so on. Deep breathing exercises like in yoga, connecting emotionally to loved ones at a deeper level, having a pet like a dog or a cat to get some unconditional love, lots of good humor and laughter, and prayer …… all of this induces a feeling of well-being and helps in good cardiovascular health.

However, if all of that is not enough, and if medication is necessary, a diuretic medication and an ACE inhibitor can be the first line of medication.

Whatever it takes, my friend, whatever it takes! Until we meet next week …. please do make your health a high priority!

Take care …. of yourself and your health ….

Dr. Ajit Damodaran