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By B. Kalan. Central State University.

The three major endothelin thought to serve as a clearance mechanism for the re- peptides are all composed of 21 amino acids purchase modafinil 100 mg fast delivery. Increases in endothelin levels have been re- dase inhibitors generic 200 mg modafinil with visa, inhibit the enzymatic activity of ACE ported in patients with vasospastic buy cheap modafinil 200mg on line, hypoxic order 200mg modafinil visa, and isch- and neutral endopeptidase proven modafinil 200mg, the enzyme responsible for emic diseases. The end result is receptors have differing affinity for the three endothe- a reduction in the synthesis of angiotensin II and an in- lin peptides. Selective and nonselective endothelin re- crease in the circulating level of natriuretic peptides ceptor antagonists are in development for potential use such as ANP. Omapatrilat, a vasopeptidase inhibitor, is in the treatment of hypertension and other disorders as- under study for the treatment of hypertension and con- sociated with increased vascular resistance. Natriuretic Peptides Nitric Oxide Natriuretic peptides are naturally occurring substances Nitric oxide is a small, unstable free radical that acts as a in the body that oppose the activity of the renin– biological messenger in many physiological responses. The natriuretic peptide family con- Because it can diffuse freely in all directions from its site sists of atrial natriuretic peptide (ANP), brain natri- of origin, regulation of the activity of nitric oxide is pri- uretic peptide (BNP), and C-type natriuretic peptide marily through control of its synthesis. All three natriuretic peptides are synthesized tric oxide occurs through oxidation of the amino acid L- from cleavage of a larger precursor polypeptide. In the arginine, a reaction catalyzed by the enzyme nitric oxide ventricles and brain, the synthesis of BNP predomi- synthase (NOS), to produce nitric oxide and L-citrulline. Activation of synthesis of the inducible form 216 III DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM of NOS results in continued synthesis of nitric oxide for neurons leads to activation of the brain form of NOS several hours. The function nine, including L-Nw nitroarginine (L- NNA) and L-Nw of brain nitric oxide is thought to involve actions as methylarginine (L-NMA), both of which decrease nitric a retrograde neurotransmitter whereby nitric oxide oxide synthesis. In the cardiovascular system, nitric oxide is Even though nitric oxide is the physiological media- the biological mediator of vasodilator responses to tor of a variety of responses, excess nitric oxide is toxic to agents such as acetylcholine and bradykinin, which act many cells as a result of its role in the production of per- as receptors on endothelial cells to activate NOS and oxynitrite and resultant lipid oxidation. Diffusible nitric oxide NOS enzyme are in clinical trials for the treatment of hy- then activates guanylate cyclase in vascular smooth potension associated with septic shock. Administration muscle cells, leading to the production of cyclic guano- of low concentrations of nitric oxide through respiratory sine monophosphate (GMP) and vasodilation. In the ventilators has been implemented to treat persistent pul- brain, stimulation of N-methyl-D-aspartate receptors on monary hypertension of the newborn. L-Argenine serves as a precursor for both ACE inhibitors and AT1 receptor antagonists (A) Bradykinin is that (B) L-Citrulline (A) Both classes of drugs increase bradykinin. ACE inhibitors increase circulating bradykinin (D) Both classes of drugs decrease circulating an- levels, while AT1 receptor antagonists have no ef- giotensin II levels. The ability of con- (E) Both classes of drugs are first-choice treat- verting enzyme inhibitors to increase bradykinin ments for congestive heart failure. Angiotensin II can class of drugs in the treatment of hypertension and (A) Increase the synthesis and release of aldos- heart failure. With an ACE inhibitor, the actions of terone angiotensin II at both the AT1 and the AT2 recep- (B) Reduce the activity of the sympathetic nervous tor is decreased; however, with an AT1 receptor an- system tagonist, angiotensin II can act at the AT2 receptor. Angiotensin II has diverse physiological effects, (A) Angiotensin receptor antagonist including stimulating the synthesis and release of al- (B) ACE inhibitor dosterone from the adrenal cortex. This effect of an- (C) Aldosterone receptor antagonist giotensin II results in fluid and water retention. The (D) Bradykinin antagonist other answers are incorrect in that angiotensin II 18 The Renin–Angiotensin–Aldosterone System and Other Vasoactive Substances 217 stimulates the sympathetic nervous system, is a Atrial natriuretic peptide is synthesized by cleavage weak inotropic, contracts vascular smooth muscle, of a larger precursor polypeptide. Vasopeptidase inhibitors: A new thera- as a biological messenger in many physiological re- peutic concept in cardiovascular disease? However, the compromised liver func- eliminate his weekly soccer games because of ex- tion requires caution with any drug that requires treme shortness of breath. Therefore, either captopril edge of the renin–angiotensin system and the or lisinopril would be an appropriate ACE inhibitor specifics concerning drugs targeted against this sys- in the treatment of this patient. AT1 receptor antag- tem, provide a rationale for use of two drugs to onists are indicated for the treatment of hyperten- treat the cardiovascular disease in this patient. In addition, the sartan, and telmisartan do not require liver metabo- patient has compromised liver function, limiting the lism to produce an active compound. Triggle D R U G L IS T GENERIC NAM E PAGE GENERIC NAM E PAGE Amlodipine 218 Nifedipine 218 Diltiazem 218 Nimodipine 218 Felodipin 218 Nisoldapine 218 Isradipine 220 Verapamil 218 Nicardipine 218 The agents commonly called the calcium channel ine (Cardene), felodipine (Plendil), nisoldipine (Sular), blockers comprise an increasing number of agents, includ- and am lodipine (Norvasc). These agents differ from ing the prototypical verapamil (Calan, Isoptin), nifedipine nifedipine principally in their potency, pharm acokinetic (Adalat, Procardia), and diltiazem (Cardizem). Nim odipine has agents are a chemically and pharmacologically heteroge- selectivity for the cerebral vasculature; am lodipine ex- neous group of synthetic drugs, but they possess the com- hibits very slow kinetics of onset and offset of blockade; mon property of selectively antagonizing Ca move- and felodipine and nisoldipine are vascular-selective ments that underlie the process of excitation–contraction 1,4-dihydropyridines.

Coarctation—A narrowing of the aorta that is Other dangerous conditions associated with bicuspid often associated with bicuspid aortic valve cheap 100 mg modafinil overnight delivery. People with aortic aneurysms usually do not experi- Echocardiogram—A non-invasive technique discount modafinil 200mg online, ence symptoms unless the aneurysm ruptures discount modafinil 100 mg otc, but people using ultrasonic waves order 100 mg modafinil with mastercard, used to look at the various with aortic dissection experience tearing back pain order modafinil 100 mg online. Aortic aneurysm rupture and aortic dissection are very Electrocardiogram (ECG, EKG)—A test used to dangerous and can rapidly lead to death if not promptly measure electrical impulses coming from the heart treated. Diagnosis Endocarditis—A dangerous infection of the heart valves caused by certain bacteria. Any of the symptoms of aortic stenosis, aortic regur- gitation, or endocarditis should prompt a search for an Heart valve—One of four structures found within underlying malformation of the aortic valve. Aortic the heart that prevents backwards flow of blood stenosis or regurgitation is diagnosed by a combination into the previous chamber. The Murmur—A noise, heard with the aid of a stetho- earliest sign of aortic valve problems is a murmur (the scope, made by abnormal patterns of blood flow sound of abnormal patterns of blood flow) heard with a within the heart or blood vessels. When the valve has high levels of calcium Reduced penetrance—Failing to display a trait or deposits, a characteristic clicking sound can also be heard disease despite possessing the dominant gene that with the stethoscope just as the stiff valve attempts to determines it. Later signs include a large heart seen on x ray or by a special electrical test of the heart, called an ECG or Sporadic—Isolated or appearing occasionally with EKG (electrocardiogram). If these signs are present, it suggests that the aortic Stethoscope—An instrument used for listening to valve may be damaged. The next test to be performed is sounds within the body, such as those in the heart echocardiography, a method that uses ultrasound waves or lungs. Often, only two cusps are seen on the aortic valve during then use different tests to identify which species of bac- the echocardiography, confirming a diagnosis of bicuspid teria is present so that appropriate treatment can be aortic valve. The diagnosis of endocarditis is also confirmed Endocarditis is diagnosed by demonstrating the pres- by using echocardiography to look for bacterial growths ence of bacteria in the blood stream. During the echocardiography, a taking blood from the patient and growing the bacteria on bicuspid valve is often seen and explains the tendency to plates with specialized nutrients. GALE ENCYCLOPEDIA OF GENETIC DISORDERS 155 This view of a human heart specimen clearly shows the structure of a bicuspid aortic valve. However, in patients with any compli- Patients with endocarditis need to be hospitalized cation of valve damage, as previously discussed, treat- and treated with high does of antibiotics given through a ment may be necessary. Damage done to the valve by the bacteria may make it necessary for a valve replacement In younger patients who have aortic stenosis, a pro- procedure to be performed after the patient has recovered cedure can be performed in which a small balloon is from the infection. The balloon is then inflated, creating a In any case, people who have been identified as hav- bigger opening for blood to pass. Alternatively, an “open ing bicuspid aortic valve should be followed regularly by heart” procedure can be performed to cut the valve into a a cardiologist, with possible consultation with a cardio- more normal configuration. The function of the bicuspid aortic temporary, and later in life the patient, as well as any valve should be followed through the use of echocardio- adult with advanced aortic stenosis, will most likely graphy, and the state of the heart itself should be followed require aortic valve replacement. Valve replacement is an “open heart” operation It should be noted that children with aortic stenosis where the original malformed valve is removed and may not be able to engage in vigorous physical activity replaced with a new valve. This new valve can come from without the risk of cardiac arrest and should consult their a human donor who has died, or from cows or pigs, or physician. These valve should receive antibiotics prior to any dental pro- valves function well, but may need to be replaced after 10 cedure or surgery; these procedures may allow bacteria to to 20 years, as they wear out. Another option is to use an enter the blood stream and could result in endocarditis if artificial valve made of metal, plastic, or cloth. It is better to perform the oper- the fluid can be used for a variety of tests to obtain ation before any of the advanced symptoms (shortness of information about genetic disorders and other breath, chest pain, fainting spells) develop; in patients medical conditions in the fetus. If a person with advanced symptoms Autosomal recessive—A pattern of genetic inheri- chooses not to undergo surgery, the risk of death within tance where two abnormal genes are needed to three years is more than 50%. Resources Co-enzyme—A small molecule such as a vitamin that works together with an enzyme to direct a PERIODICALS biochemical reaction within the body. Mutation—A permanent change in the genetic WEBSITES material that may alter a trait or characteristic of “Bicuspid Aortic Valve. National Center for Biotechnology Infor- an individual, or manifest as disease, and can be mation. Oren Traub, MD, PhD Description Biotin is essential as a co-factor (co-enzyme) for the reactions of four enzymes called carboxylases.

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