Neurogenic hypertension

The pathogenesis of neurogenic hypertension appears to be somewhat as follows ... 

In over half of a series of 33 samples of arterial blood of hypertensives, the amine picrates measured in terms of isoamylamine were higher than in twelve of fifteen normal ones, and in nine cases were more than 10 mg. per liter. The normal range was 0 to 7.0 mg., only three being greater than 3 mg. In a second series, the results, expressed in terms of units of color, showed high values in two of twelve normal subjects, seven of fourteen patients with neurogenic hypertension, and eleven of thirteen with renal hypertension. The color-concentration curves obtained from picrates of various amines, however, differed in their slopes therefore the amount of color found was no true indication of the actual concentration of any one amine. 

In order to integrate further some of the various reactions mentioned, and to detect its presence by other methods, the vessels of the rat s mesoappendix were employed as a test object (Chambers-Zweifach preparation, 12). A good correlation between the presence of a vasoexcitor material-like substance in the extracts and the presence of hypertension was found. When the whole rat was used for assay, a much cruder index, sizable quantities of active pressor material were isolated from the blood only of those patients showing at least a degree of renal impairment (lessened ability to concentrate urine, etc.). In general it may be stated unequivocally that patients with severe hypertension have in their arterial blood extractable substances which are pressor for the rat there are less or undemonstrable amounts in blood of less severe or neurogenic hypertensive patients there is little or none in blood of normotensive subjects a vasoexcitor material-like activity is exerted by blood from most hypertensive patients adenyl compounds, having a depressor action, present in extracts of blood are less prevalent in those from hypertensive patients the active rat pressor material (pherentasin) is probably aminelike in nature, is not a protein, but may be a simple peptide or an amine. 

An interesting reaction to intradermal histamine has been described (55), which, while not a pressor substance, appears to reproduce certain symptoms and signs encountered in hypertensive subjects. Histamine has a renal action similar to epinephrine (47), constricting efferent arterioles. In neurogenic hypertensive patients it also produces the hypertensive diencephalic syndrome." Whether this reaction is direct, or indirect through some other mechanism, is obscure. 

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. 

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. 

One of the distinguishing characteristics of uncomplicated neurogenic hypertension is its dramatic response to sympathectomy or to chemical blockade of the sympathetic nervous system. Complete sympathectomy results in an immediate reduction in the blood pressure to normal or to subnormal levels with a gradual return to normotensive or slightly higher levels over a period of 1 to 2 months (41, 48, 4)- Moderator nerve section or increased intracranial pressure usually fails to increase the blood pressure in completely sympathectomized animals and if a rise is elicited it is relatively slight and develops slowly (5, 27, 41) ... 

In contrast to neurogenic hypertension, the role of adrenergic factors in experimental renal hypertension is obscure. The sequence of events by which interference with renal hemodynamics leads to elevation of the systemic blood pressure has been carefully studied and has been shown to be independent of nervous mechanisms (see 11, 35). Sympathectomy does not prevent the development of renal hypertension and induces only slight and irregular reductions in pressure in renal hypertensive animals (3, 28, 55, 97). 

Figure 2. Possible Contributions to Maintenance of Systemic Arterial Pressure during Neurogenic Hypertension and Its Subsequent "Cure by Sympathectomy or Adrenergic Blockade A. Normal...

Some N-substltuted phenoxyethylamlnes (Xll) have been prepared and their hypotensive effects evaluated in anesthetized normotensive cats and neurogenically hypertensive dogs. A study of the structure-activity relationships revealed that the 2-(2-methoxyphenoxy) ethylamino moiety is necessary for maximum effect. Three members of the series XII, R = CHaCHOHCHaOCHgCH CHa, (CHa)4C6H40CH3 (CHa)sOCsH3-2,5... 

Serotonin is usually a pressor substance, but there are times when it is a pure depressor agent. To get around this difficulty, McCubbin and I felt ourselves forced into creating the word amphibaric to describe this situation. Then we found that whether it raises, or lowers, blood pressure depends on the neurogenic tone at the time. If it is high, as after stimulation of the sympathetic chain or induction of neurogenic hypertension, serotonin is a depressor. In short, there was clear sympathetic inhibition. 

Compound VI (USVP-D177) was orally active in reducing blood pressure of neurogenic hypertensive dogs. The effect appeared to be a combination of vasodilation and reduction in cardiac output. 

A number of methods have been described for the production of persistent hypertension in animals. Neurogenic hypertension follows the impairment of cerebral blood supply. This can be achieved either through... 

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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