Hypertension, essential, role

Oparrl S, Horton R, Wilkins LH, Irvin J, Hammett DK. Antihypertensive effect of enalqnil in essential hypertension role of prostacyclin. AmJ Med Sci (1987) 294,395-402. 

Felder, R. A., and Jose, P. A. (2006) Mechanisms of disease the role of GRK4 in the etiology of essential hypertension and salt sensitivity. Nat. Clin. Pract. Nephrol. 2,637-650. 

Renin, angiotensin, and aldosterone play important roles in at least some people with essential hypertension. Approximately 20% of patients with essential hypertension have inappropriately low and 20% have inappropriately high plasma renin activity. Blood pressure of patients with high-renin hypertension responds well to drugs that interfere with the system, supporting a role for excess renin and angiotensin in this population. 

A relatively new and promising area of research concerns the role of inadequate dietary calcium in the development of essential hypertension or high blood pressure (Villar et al. 1986 Karanja and McCarron 1986 Resnick 1985 NDC 1984A.B McCarron 1985, 1983, 1982 McCarron et al. 1982). While most reports relating diet to hypertension have emphasized sodium, it appears that only a small proportion of the U.S. population is genetically sodium sensitive and that for the majority, dietary sodium intake has little effect on blood pressure. As discussed below, inadequate calcium intake, either alone or in combination with other factors, appears to predispose to high blood pressure by a mechanism(s) as yet unknown. 

Considerable progress has been made in the development of agents capable of producing a specific and effective blockade of responses to sympatho-adrenal activity. Three groups of compounds show particular promise—the jd-haloalkylamines, the dihydro ergot alkaloids, and the imidazolines. However, lack of information regarding the role of sympatho-adrenal factors in the etiology of essential hypertension prevents a definitive evaluation of their potential usefulness in the therapy of this condition. 

Neurogenic renal vasoconstriction, with consequent activation of the renin-angio-tonin mechanism, is not a major factor in most cases of neurogenic hypertension evidence for this is seen in the limited fall in blood pressure which follows renal denervation (41, 54) and the failure of prior nephrectomy to alter the pressor response to moderator nerve section (95). However, neurogenic renal vasoconstriction may be adequate to produce a sustained hypertension after other body structures have been sympathetically denervated (42, 44)) and it is possible that neurogenic renal vasoconstriction may play a significant role in the development of essential hypertension. 

On the basis of the above discussion it would appear that the role of adrenergic blockade in the treatment of hypertension, with the exception of isolated cases clearly due to sympatho-adrenal factors, is negligible. However, the possibility remains that neurogenic factors may be involved in the early stages of human essential hypertension. Certain psychic components are known to be involved in the development of hypertension and it is possible that emotionally activated neurogenic factors may cause repeated episodes of renal vasoconstriction and ischemia, which finally lead to the development of local organic... 

A clinical diagnosis of essential hypertension usually carries no connotation as to the etiology of the condition, and yet the preponderance of literature directing attention to the etiological role of one or another organ in the production of hypertension very often influences our everyday thoughts on the subject. 

Fenton-like reactions play an important role in a variety of catalytic and biological processes. In biology these reactions are believed to be the main source of reactive oxygen species (ROS) in the cell causing a variety of diseases, eg cancer, arteriosclerosis, essential hypertension, Alzheimer s disease, amyloidosis, osteoarthritis [9],... 

Albrecht FE, Drago J, Felder RA, Printz MP, Eisner GM, Robillard JE, Sibley DR, Jose PA (1996) Role of the D-1A dopamine receptor in the pathogenesis of essential hypertension. J Clin Invest 97 2283-2288. 

The KO models confirm the essential adaptive roles of oq-ARs in the heart, where the A and the B are required for chronic trophic or nutritional effects that depend ultimately on anabolic, transcriptional, metabolic, and antiapoptotic processes. The A and the B mediate inotropic effects, which depend on the preparation, and the D causes coronary vasoconstriction. The distinct roles of the A and the B in heart remain to be worked out. Clinically, the results emphasize concern about the use of nonselective oq-antagonist drugs in patients with hypertension or prostate disease. On the other hand, D-selective antagonists might have advantages. 

To date, no associations have been established for the Lys251 c aAR polymorphism and clinical phenotypes in which cy2aARs are thought to play a role. One case-control study has been performed to ascertain the frequency of this polymorphism in patients with essential hypertension (95) however, considering the gain-of-function phenotype of the polymorphic receptor and the known centrally mediated hypotensive functions of the c aAR (100), results showing a lack of association with this polymorphism and essential hypertension are not surprising. 

Vascular endothelium and smooth muscle play important roles in regulating blood vessel tone and BP. These regulating functions are mediated through vasoactive substances that are synthesized by endothelial cells. It has been postulated that a deficiency in the local synthesis of vasodilating substances (e.g., prostacyclin and bradykinin) or excess vasoconstricting substances (e.g., angiotensin II and endothelin I) contribute to essential hypertension, atherosclerosis, and other diseases. 

It is generally assumed that the intracellular content of sodium in vascular smooth muscle is increased in essential hypertension. Although the major role of aldosterone (see Figure 17) in the regulation of blood pressure is a renal one,... 

It is generally assumed that the intracellular content of sodium in vascular smooth muscle is increased in essential hypertension. Although the major role of aldosterone in the regulation of blood pressure is a renal one, it may also be involved in some extrarenal effects responsible for the regulation of body fluid and blood pressure. Recent studies have suggested that vascular walls specifically bind to aldosterone and that aldosterone has a direct vasoconstrictive effect on vascular smooth muscle in vitro. Indeed, canrenoate potassium (Soldactone S), an aldosterone antagonist, reduces blood pressure (Figure 24). 

Vasopressin appears to help maintain arterial blood pressure during episodes of severe hypovolemia/hypotension. There is no convincing evidence for a role of vasopressin in essential hypertension. The effects of vasopressin on the heart (reduced cardiac output and heart rate) are largely indirect and result from coronary vasoconstriction, decreased coronary blood flow, and alterations in vagal and sympathetic tone. Some patients with coronary insufficiency experience angina even in response to the relatively small amounts of vasopressin required to control diabetes insipidus, and vasopressin-induced myocardial ischemia has led to severe reactions and even death. 

An enormous amount of new information relevant to the role of insulin resistance in human disease had appeared since the introduction of the concept of Syndrome X, and the abnormalities related to insulin resistance have broadened considerably. At the same time, it has become clear that the adverse clinical outcomes associated with insulin resistance extend far beyond type 2 diabetes and CVD. For example, in addition to type 2 diabetes and CVD, insulin-resistant individuals are at increased risk to develop essential hypertension, PCOS, nonalcoholic fatty liver disease, congestive heart failure. 

---