Calcium, hypertension muscle contraction

Amlodipine is a calcium channel blocker used to treat hypertension and angina pectoris. Calcium channel blockers block the passage of calcium, an essential factor in muscle contraction, into the heart and smooth muscles. Such blockage interferes with the contraction of these muscles, which in turn dilates the veins that supply blood to them. This reduces blood pressure. 

IMidodrine Activates phospholipase C, resulting in increased intracellular calcium and vasoconstriction Vascular smooth muscle contraction increasing blood pressure (BP) Orthostatic hypotension Oral prodrug converted to active drug with a 1-h peak effect Toxicity Produces supine hypertension, piloerection (goose bumps), and urinary retention... 

The calcium ion liquid-membrane electrode is a valuable tool for physiological investigations because this ion plays important roles in such processes as nerve conduction, bone formation, muscle contraction, cardiac expansion and contraction, renal tubular function, and perhaps hypertension. Most of these processes are influenced more by the activity than the concentration of the calcium ion activity, of course, is the parameter measured by the membrane electrode. Thus, the calcium ion electrode (and the potassium ion electrode and others) is an important tool in studying physiological processes. 

The synthesis of this tritium-labelled dihydropyridine derivative, 137, a powerful anti hypertensive agent attenuating smooth muscle and cardiac muscle contractions by blocking the influx of calcium ions into vascular smooth muscle cells, has been carried out " " by preparing initially the 3-nitrobenzaldehyde[4,6- H] 138 of high specific activity in the four steps shown in equation 58. It was then used in the Hantzsch... 

Pozzan T, Rizzuto R, Volpe P, Meldolesi J (1994) Molecular and cellular physiology of intracellular calcium stores. Physiol Rev 74 595-636 Raeymakers L, Wuytack F (1996) Calcium pumps. In Barany M (ed) Biochemistry of smooth muscle contraction. Academic Press, San Diego, pp 241-253 Rembold CM (1990) Modulation of the [Ca " ] sensitivity of myosin phosphorylation in intact swine arterial smooth muscle. J Physiol 429 77-94 Rembold CM, Weaver BA (1990) [Ca ], not diacylglycerol, is the primary regulator of sustained swine arterial smooth muscle contraction. Hypertension 15 692-698 Shimada T, Somlyo AP (1992) Modulation of voltage-dependent Ca channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle. J Gen Physiol 100 27-44... 

In addition to their normal physiological functions (muscle contraction, neurotransmitter release, gene transcription, etc.), calcium channels are also implicated in human disorders (cerebellar ataxia, epilepsy, hypertension, arrhyth-... 

Calcium ions Movement of Ca ions from the extracellular environment into the cytosol is achieved via calcium ion channels. An increase in the number of Ca " ion channels that are open in cells of smooth or cardiac muscles stimulates contraction. Excessive rates of entry can, however, cause problems. For example, increased entry of Ca ions into vascular smooth muscle increases contraction which rednces the diameter of blood vessels which can lead to hypertension (Chapter 22). 

Endothelins are a family of vasoactive peptides secreted by endothelial cells. The three major endothelin peptides are all composed of 21 amino acids. Endothelins are the most potent vasoconstrictors known. Contraction of vascular smooth muscle in response to endothelin is associated with an increase in intracellular calcium. Increases in endothelin levels have been reported in patients with vasospastic, hypoxic, and ischemic diseases. The two identified isoforms of endothelin receptors have differing affinity for the three endothelin peptides. Selective and nonselective endothelin receptor antagonists are in development for potential use in the treatment of hypertension and other disorders associated with increased vascular resistance. 

Epidemiologic, experimental, and in vitro mechanistic data indicate that lead exposure elevates blood pressure in susceptible individuals. In populations with environmental or occupational lead exposure, blood lead concentration is linked with increases in systolic and diastolic blood pressure. Studies of middle-aged and elderly men and women have identified relatively low levels of lead exposure sustained by the general population to be an independent risk factor for hypertension. In addition, epidemiologic studies suggest that low to moderate levels of lead exposure are risk factors for increased cardiovascular mortality. Lead can also elevate blood pressure in experimental animals. The pressor effect of lead may be mediated by an interaction with calcium mediated contraction of vascular smooth muscle, as well as generation of oxidative stress and an associated interference in nitric oxide signaling pathways. 

Intoxication with vitamin D causes weakness, nausea, loss of appetite, headache, abdominal pains, cramps, and diarrhea. More seriously, it also causes hypercalcemia, with plasma concentrations of calcium between 2.75 to 4.5 mmol per L, compared with the normal range of 2.2 to 2.5 mmol per L. At plasma concentrations of calcium above 3.75 mmol per L, vascular smooth muscle may contract abnormally, leading to hypertension and hypertensive encephalopathy. Hypercalciuria may also result in the precipitation of calcium phosphate in the renal tubules and hence the development of urinary calculi. Hypercalcemia can also result in calcinosis - the calcification of soft tissues, including kidneys, heart, lungs, and blood vessels. This is assumed to be the result of increased calcium uptake into tissues in response to excessive plasma concentrations of the vitamin and its metabolites. 

Trandolapril/verapamil hydrochloride is an antihypertensive combination, which Trandolapril reduces formation of the vasopressor hormone angiotensin II by inhibiting angiotensin-converting enzyme (ACE), resulting in decreased BP and reduced sodium reabsorption and potassium retention. Verapamil inhibits movement of calcium ions across cell membrane, resulting in depression of mechanical contraction of myocardial and vascular smooth muscle and depression of both impulse formation (automa-ticity) and conduction velocity. They are indicated in the treatment of hypertension. 

Calcium antagonists (Figure 4.3) are agents which block the flow of calcium ions into cardiac and vascular smooth muscle when they are stimulated to contract. They have value as vasodilators for use in hypertension and also reduce blood flow resistance and cardiac workload in the treatment of angina. Verapamil (Knoll Pfizer, 1967) is also used as an antiarrhythmic because of its effects on ion channels in the heart s electrical conduction system. Nifedipine (Bayer, 1977) is among the world s top 25 drugs and is the forerunner of several agents of the dihydropyridine class. 

Calcium channel blockers, also known as calcium antagonists, are a class of hypertension drugs that inhibit the influx of calcium ions through the cell membrane. A decrease in calcium ions results in less contraction of the cardiac and vascular muscles. There is an increase in the diameter of the arteries. This vasodilatation results in a lowering of the blood pressure. Despite their name, calcium channel blockers do not plug the hole and physically block the calcium ion channel. Rather, they bind to specific receptor sites [30]. Examples of calcium channel blockers are nifedipine (Procardia , Pfizer), nicardipine hydrochloride, amlodipine besylate sulfonate (Norvasc , Pfizer) and verapamil hydrochloride (Calan , Pfizer). Verapamil has a chiral carbon but is administered as a racemic mixture. 

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