Essential Human Hypertension

The circulatory status of patients with essential hypertension resembles fundamentally the hypertension produced in animals. There is also clinical evidence that the kidneys are diseased in many patients with hypertension. Fishberg (45) and Bell and Clawson (10), as well as Moritz and Oldt (115), have found oi anic arteriolar disease in the kidneys of a majority of patients who had essential hypertension with or without signs of disturbed renal excretory function. Furthermore, renal ischemia was found to be present in many hypertensive patients (169). This ischemia seemed to be the result of the presence of vasoconstrictor substances in the blood, since it was readily reversible by agents which produce renal hyperemia in normal persons. Smith, Goldring, and Chasis (169) investigated the impairment of renal blood flow in 21 hypertensive patients. In none of these patients did the authors find unilateral impairment of the renal blood flow. 

Smith and co-workers interpreted this result as evidence against the theory that essential hypertension starts with an obstruction to renal circulation. It is their opinion that such an obstruction would not be distributed symmetrically and would not affect the renal blood flow symmetrically. The final conclusion of these authors is  

The search for a pressor substance in the blood of hypertensive patients has yielded many conflicting reports, too numerous to be discussed here. It seems to be quite difficult to avoid the appearance of pressor substances even in blood taken from normotensive persons (111). Dexter and Haynes (38) confirmed in hypertensive patients the earlier results of Dell -Oro and Braun-Menendez (36) on hypertensive dogs. As in dog blood, renin was found in human blood only when the blood pressure was rising acutely none was found in the blood of thirteen patients with chronic essential hypertension of all degrees of severity. Taquini and Fasciolo (175a) also found no renin in the plasma of twenty-three patients with essential hypertension. Hypertensin was recovered from the plasma of patients to whom the pressor agent had been given intravenously (58) it was not foimd, however, in ultra filtrates of plasma from hypertensive patients (58). 

Gregory and co-workers (58-61) have presented further evidence to show that the renin-hjrpertensin system is apparently not responsible for the maintenance of chronic essential hypertension in man. A profound drop in blood pressure was observed in patients with essential hypertension during spinal anesthesia. During this period, however, there was nc change in the response of these patients toward the injection of hyperten- 

Renin and hypertensin have not been found in the blood of patients suffering from essential hypertension. However, hypertension in man is rarely diagnosed and classified in the initial stage of the disease. In view of the results with late hypertension in animals, the absence of renin in the blood of patients with well-established hypertension is not surprising. It is quite likely that these patients were already in the second phase of the disease, neurogenic hypertension, when their plasma was examined for the presence of renin and hypertensin. Failure to find these substances does not disprove the renal origin of essential hypertension. 

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From what has already been published, and from what is contained in this symposium, it is abundantly clear that at least the early period of the hypertension which develops after constriction of the main renal arteries of animals is of humoral origin. The difficulty has been, and still is, the direct application of what has been learned about experimental renal hypertension to the problem of the pathogenesis of human essential hypertension. Of the greatest importance would be the determination of the exact cause of the relatively long period of experimental hypertension and of human hypertension in which, up to the present time, the existence of a humoral mechanism has not been proved. 

Because of the many dissimilarities between human essential hypertension and experimental neurogenic hypertension, studies of the latter have been relegated to the background in recent years in favor of work on experimental renal hypertension, which much more closely resembles essential hypertension (Table I 11, 35, 64, 77). Nevertheless, a careful analysis of neurogenic hypertension is important as a basis for the recognition or exclusion of neurogenic factors in human hypertension. 

In summarizing evidence for the participation of deranged sympatho-adrenal ( neurogenic ) factors in human hypertension, it must be concluded that such factors have been conclusively demonstrated only in cases of pheochromocytoma, central nervous system trauma, and increased intracranial pressure. There is presumptive evidence that neurogenic factors may be important during the early, labile phases of essential hypertension and that the effects of this early sympatho-adrenal activity may lead to a persistent hypertension on a renal basis later in life. However, the development of hypertension through this or any other mechanism occurs only in individuals predisposed by some completely unknown, but probably hereditary, influence. 

At the present time, pheochromocytoma and intracranial lesions are the only causes of human hypertension which are definitely known to involve overactivity of the sympatho-adrenal system. However, presumptive evidence is accumulating to indicate that neurogenic factors may be involved in early essential hypertension, and it is possible that adequate adrenergic blockade early in the course of such hypertension may be effective in aborting its development. Only additional evidence regarding the etiology of essential... 

Howie AJ (1996) Benign essential hypertension and kidney damage a histopathologist s view, journal of Human Hypertension 10 691-694. 

Campese VM, Amar M, Anjali C et al. Effect of L-arginine on systemic and renal haemodynamics in salt-sensitive patients with essential hypertension. Journal of Human Hypertension 1997 11 527-532. 

Corvol P, Persu A, Gimenez-Roqueplo A-P, Jeunemaitre X. Seven lessons from two candidate genes in human essential hypertension. Hypertension 1999 33 1324-1331. 

The possible involvement of free radicals in the development of hypertension has been suspected for a long time. In 1988, Salonen et al. [73] demonstrated the marked elevation of blood pressure for persons with the lowest levels of plasma ascorbic acid and serum selenium concentrations. In subsequent studies these authors confirmed their first observations and showed that the supplementation with antioxidant combination of ascorbic acid, selenium, vitamin E, and carotene resulted in a significant decrease in diastonic blood pressure [74] and enhanced the resistance of atherogenic lipoproteins in human plasma to oxidative stress [75]. Kristal et al. [76] demonstrated that hypertention is accompanied by priming of PMNs although the enhancement of superoxide release was not correlated with the levels of blood pressure. Russo et al. [77] showed that essential hypertension patients are characterized by higher MDA levels and decreased SOD activities. 

Bonnardeaux, A., Davies, E., Jeunemaitre, X., et al. (1994) Angiotensin-11 type-1 receptor gene polymorphisms in human essential-hypertension. Hypertension. 24, 63-69. 

It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud s syndrome. Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins. 

Essential though sodium is to the normal functioning of the human body, there has been considerable concern over the last few years, about the amount of salt in the diet. This concern centers mainly on possible relationship between salt and hypertension (high blood pressure). 

If one considers H3 receptor agonists as potential drugs, one has to realize that H3 heteroreceptor-mediated effects are frequently small or moderate. In addition, one has to take into consideration that the release of at least six transmitters is affected and that the effects occur in at least six regions of the CNS (Fig. 1). On the other hand, it is so far unknown whether all the examples of H3 heteroreceptors identified in animals also occur in humans. Moreover, one must be cautious when extrapolating from in vitro data to the situation in vivo. To give an example. Clonidine, which affects presynaptic a2-adrenoceptors on several types of neurones and in a variety of CNS regions, became a very useful drug for the treatment of essential hypertension and for some other indications. 

Urohypertensin (1) was isolated from urine many years ago, and resembles in some respects Lockett s base A, except that it was not, like base A, precipitated with mercuric chloride. Bain (4) thought that isoamylamine, which he found in human urine, was urohypertensin. Lockett was unable to find isoamylamine in urine, although von Euler and Sjostrand (22) have stated that it is present in decreased amounts in essential hypertension. These pressor bases are worth further study, especially their relation to amines. 

In human essential hypertension also, sympathectomy or blockade of the sympathoadrenal system brings about an equivocal response. There is little doubt that various degrees of surgical sympathectomy may produce a prolonged reduction in blood pressure in certain selected cases (43, 81, 82, 89), but the response is highly variable and the degree of benefit attributed to the procedures employed may depend to a considerable extent upon an evaluation of the natural course of the disease (see 79). 

The highly variable blood pressure responses to adrenergic blockade in cases of experimental renal hypertension and human essential hypertension, particularly those... 

Column C represents a case in which sympathetically mediated renal vascular tone is assumed to be a significant factor in maintaining the elevated pressure, and column D depicts possible changes in the few cases of human essential hypertension in which a continued fall in pressure is noted for some time after sympathectomy, perhaps also on the basis of altered renal blood flow. Column E represents a common result of sympathectomy or adrenergic blockade in renal and essential hypertension this result may or may not be preceded by some early fall in pressure such as illustrated in column C. 

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... 

Dibenamine has been employed with excellent results in the diagnosis and preoperative therapy of pheochromocytoma (90, 91). The pressor response evoked by the histamine test in these patients is completely blocked and reversed, and the injection of Dibenamine at 72-hour intervals has been found to provide complete symptomatic relief. In human essential hypertension, therapy with Dibenamine produces a very significant fall in both systolic and diastolic pressures in some patients (see 12). In severe hypertension, particularly the malignant form, the drug has been found to lower the blood pressure significantly in most cases, but rarely to return it to the normotensive range. However,... 

In the high-renin Goldblatt two-kidney, one-clip renal hypertensive rat, immediate pressure lowering was observed with orally administered captopril (30 mg/kg), and an antihypertensive effect could be maintained for at least 10 months. Spontaneously hypertensive rats, which are considered to be a model of essential hypertension in humans, also responded to oral captopril, but a dose of 100 mg/kg was required. As expected in both models of hypertension, the addition of diuretics enhanced the antihypertensive activity of captopril (105). 

McLellan AR, Milligan G, Houslay MD, Connell JM. 1993. G-proteins in essential hypertension a study of human platelet plasma membranes. J Hypertens 11 543—549. 

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