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The substance P-like immunoreactivity (SPLIR) of plasma and adrenal medulla from spontaneously hypertensive (SHR) and normotensive WKY rats was measured by a sensitive and highly specific radioimmunoassay for substance P (SP). With increasing age the level of substance P in the adrenal medulla decreased, whereas the SP content of the plasma remained constant in both groups. The SPLIR in plasma of SHR was significantly lower than in normotensive WKY rats. After acute stress the SPLIR, especially of the adrenal medulla of WKY rats, increases, and decreases in SHR. The reason for this different behaviour is discussed and it is assumed that hyperreactions in the sympathetic system may be responsible.

Substance P (SP) plays an important role in central nervous and peripheral blood pressure regulation. Its effects include modulating influence on the adrenergic system and inhibition of stress-induced plasma noradrenaline increase in animal studies. In patients with essential hypertension (n = 45, WHO stages 1 and 2) the SP-like immunoreactivity (SPLIR) was found significantly (p less than 0.01) lower (1.36 +/- 0.23 pg/100 microliters) than in 24 normotensive subjects (4.54 +/- 0.72 pg/100 microliters). Furthermore, the influence of a mental stress test on SPLIR was investigated in patients with essential hypertension (n = 11, WHO stage 1) and compared with nine normotensive subjects. Whereas in normotensive subjects plasma SP increased under a standardized mental arithmetic test (4.03 +/- 0.48 to 4.74 +/- 0.56 pg/100 microliters), in hypertensive patients a decrease of SP from lower baseline levels (2.85 +/- 0.54 to 2.57 +/- 0.54 pg/100 microliters) was demonstrated. The significantly different changes of plasma SP in normotensive and hypertensive subjects under mental stress conditions had the opposite direction in comparison with the adrenergic reaction [higher and prolonged increase of plasma noradrenaline (NA) in the hypertensive group]. Under antihypertensive drug treatment with prazosin (4.5 mg/day, n = 10) or with captopril (450 mg/day, n = 10) an increase of plasma SP was registered. The results support the participation of SP in the pathogenesis of human hypertension and in therapeutic mechanisms. Lower plasma levels and decreased responsiveness of SP possibly represent the enhanced stress sensitivity in primary hypertension.

This paper presents results on the function of the adrenal medulla, especially the influence of substance P (SP) on the cholinergic-adrenergic interaction. Interconnections between the function of SP and its role in the development and maintenance of hypertension as well as its role in stress and adaptation are investigated. Substance P acts only in situations with an increased nervous activity, for example, after stress-induced activation of the pituitary-adrenal and sympathetic-adrenal axis. Substance P normalizes stress-induced disorders by maintaining homeostasis in the catecholamine system. The basis of the antistress effect is the modulation of both biosynthesis and release of catecholamines in the adrenals. The homeostasis effect of SP, as well as the antistress effect do not require the complete sequence of the molecule. The N-terminal SP fragment is fully active and has no side effects.

Patients with essential hypertension (n = 45) had significantly lower substance P plasma levels (13.6 +/- 2.30 pg/ml) in comparison with a group of 24 normotensive subjects (45.4 +/- 7.18 pg/ml) analyzed by radioimmunoassay. Prazosin treatment for 2 weeks with 4.5 mg/day enhanced the substance P plasma level depending on its antihypertensive effect. Norepinephrine concentration in plasma was also elevated by prazosin. Dipeptidylpeptidase IV, dopamine-beta-hydroxylase and plasma renin activity were not changed significantly. The results indicate the participation of substance P in pathophysiological processes of human essential hypertension.

The influence of chronic immobilization on blood pressure and on substance P-like immunoreactivity (SPLIR) in blood plasma was examined in 11-week-old male spontaneously hypertensive rats (SHR) and male normotensive Wistar Kyoto rats (WKY). In SHR chronic immobilization caused a stop of the genetically fixed development of hypertension at the level already reached. Also, SPLIR in blood plasma was lower compared with a SHR control group without immobilization. In WKY rats chronic immobilization has no influence on blood pressure and SPLIR. The observed variations in SPLIR and blood pressure under the influence of chronic immobilization is discussed in relation to a possible function of substance P in the development of hypertension.