Changes in the intracellular pH (pH(i)) of rat peritoneal mast cells were studied using the fluorescent probe BCECF. alpha-Thrombin (0.1 nM) induced a biphasic change in pH(i) consisting of an initial transient decrease and subsequent continuous increase due to stimulation of Na+/H+ exchange; the latter was inhibited by EIPA and depended on extracellular Na+. DIP-alpha-thrombin (0.1 pM-1 nM) (a catalytically inactive form with intact recognition site) induced the biphasic change in pH(i) similar to alpha-thrombin, but beta/gamma-thrombin (10-1000 pM) (a catalytically active form with denatured recognition sue) induced only the initial, acidification phase. The thrombin recognition site modulators, alpha1-thymosin and heparin, inhibited the ability of the enzyme to induce the increase in pH(i). Nigericin activated the Na+/H+ exchange in mast cells, the rate of activation decreasing with increasing alpha-thrombin concentration from 0.1 pM up to 1 nM. Activation of protein kinase C (PKC) in mast cells by 10 nM PMA caused alkalization of the cytoplasm by activation of EIPA-sensitive Na+/H+ exchange. A PKC inhibitor, H- 7, suppressed the increase of pH(i) induced by PMA or alpha-thrombin. The alpha-thrombin-induced acidification of the cytoplasm was completely blocked by SITS in Ca2+-free medium and inhibited in Ca2+-containing medium. Thus, the thrombin-induced acidification seems to be due to both Ca2+ influx and the activation of chloride current. It is concluded that the thrombin-induced activation of Na+/H+ exchange is the result of a cascade of intracellular reactions involving PKC.

An angiotensin-I-converting enzyme, captopril, was administered since birth onward to normotensive (NR) and spontaneously hypertensive rats (SHR). It produced a marked hypotensive effect in SHR only. Cardiac output and circulating blood volume were similar in intact and experimental animals, NR and SHR alike. Captopril considerably increased plasma renin activity in NR and SHR.

Renal prostaglandin activity was assessed in children and adolescents with two forms of secondary (nephrogenic) arterial hypertension: vasorenal and chronic pyelonephritis-associated hypertension. Children with vasorenal hypertension showed renal PG changes, dependent on the duration of the disease. Positive correlation between arterial BP and PGF2 excretion, and negative correlation between PGE excretion and arterial BP are suggestive of the involvement of the renal PG system in vasorenal hypertension. Children and adolescents with arterial hypertension in the presence of chronic secondary pyelonephritis demonstrated a tendency to low excretion of both PG fractions, while their ratio remained unchanged. The absence of a correlation between urinary PG excretion and arterial BP indicates that renal prostaglandins make no significant pathogenetic contribution to this type of arterial hypertension.

The effect of antiarrhythmic drugs, ritmilen and allapinin, on endogenic prostanoid and cyclic nucleotide levels was examined in patients with heart rhythm disorders. Intravenous administration of antiarrhythmic agents is shown to be accompanied with increased release of prostacyclin that has antiarrhythmic properties into myocardial outflow. Both ritmilen and allapinin promoted the predominance of prostacyclin over thromboxane, with its intrinsic arrhythmogenic properties. Ritmilen- or allapinin-induced changes in prostaglandins E and F2 alpha consisted in that PGE prevailed, as compared to PGF2 alpha. There were no significant changes in cyclic nucleotide ratios (cAMP/cGMP) in response to treatment.

Activity of monoamine oxidases (MAO) of the types A and B (substrates: 5-hydroxytryptamine, 2-phenylethylamine, tyramine) has been studied in mitochondrial fractions from brain, heart, liver and kidney of 24-week-old rats of the normotonic strain Wistar Kyoto (WKY) and spontaneously hypertonic rats (SHR). As compared with the WKY rats, in the SHR strain the activity of MAO-A in heart mitochondria was increased 1.5-1.7-fold; in liver mitochondria the activities of both MAO-A and -B were increased 2.6-2.7-fold. In brain mitochondria there was noted only slight tendency towards an increase in MAO-A (substrate: 5-hydroxytryptamine) and MAO-B (substrate: 2-phenylethylamine) activities in the SHR strain as compared with the normotonic animals of the same age. However, in experiments with tyramine as a substrate of MAO the enzymatic activity in SHR brain mitochondria was increased 1.5-fold (P less than 0.05) as compared with the WKY rats. In kidney mitochondria of SHR the activity of MAO (substrates: 5-hydroxytryptamine, 2-phenylethylamine, tyramine) did not exhibit any alterations as compared with the control WKY rats.

Adaptation to high altitude hypoxia prevents the development of arterial hypertension only in young spontaneously hypertensive rats (SHR) in the pre-hypertension stage. Adult SHR exposed to high altitude hypoxia showed no hypotensive effect. Judging by the experiments with extremities perfusion, the prophylactic effect of high altitude hypoxia in young SHR is associated with an increased number of resistant vessels. The increased ratio of the thickness of the vessel wall to the vascular lumen, however, remains unchanged probably due to the genetically determined development of hypertrophy of vascular smooth muscles.

Limb perfusion in spontaneously hypertensive rats demonstrated increased vascular resistance at maximum vasodilatation which may be related to structural specifics: the development of smooth muscle hypertrophy in resistive vessels and, obviously, decreased total number of functioning arterioles. The obtained "perfusion pressure - noradrenaline dosage" curves provide further evidence to this effect. The shift to the left shown by these curves and their greater steepness in spontaneously hypertensive rats are due to increased vascular reactivity to pressor effects.

An experimental radioisotopic study in normotensive male Wistar rats and spontaneously-hypertensive rats (SHR) of Okamoto--Aoki line demonstrated an age-related increase in the biosynthesis of prostacycline (PGI2) from 14C-arachidonic acid by pulmonary and aortal tissues of animals with normal arterial pressure. In SHRs, PGI2 production by lung homogenates did not change essentially with age, but decreased considerably in adult SHRs with stable hypertension. PGI2 biosynthesis by SHR's aortal tissue decreased with age and dropped significantly as arterial hypertension developed. In normotensive rats, the formation of thromboxane B2 (TxB2) by platelets increased with age. Platelet TxB2 biosynthesis was elevated considerably both in young and adult SHRs. Clinically, a significant increase of platelet TxB2 production from exogenous 14C-arachidonic acid was demonstrated in children with essential hypertension.