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Sumatriptan provokes, in healthy subjects as well as in those who suffer from hemicrania, a slight increase in both systolic and diastolic arterial pressure. It has also been shown to increase the pressure of pulmonary circulation and to reduce the calibre of coronary arteries. The present investigation was undertaken to study the effects of sumatriptan (75 ng/l) on isolated rabbit hearts. Fifteen isolated rabbit hearts, perfused according to Langerdoff's procedure, were divided into two groups: Group I (5 hearts), perfused with Krebs-Henseleit solution, as a control, and Group II (10 hearts), perfused with Krebs-Henseleit mixed with sumatriptan succinate (75 ng/l). After 30 min of perfusion, the basal values of heart rate (HR) dp/dt, systolic ventricular pressure (SVP), diastolic ventricular pressure (DVP) and coronary flow (CF) were measured. The above values in either control or treated hearts were measured 5, 15, 30, 45, 60 min after recording the baseline values. HR, SVP, DVP, dp/dt and CF did not show significant differences in the two groups. The present data suggest that sumatriptan does not exert any action on isolated rabbit hearts.

Background: During heart failure, due to increased level of circulating norepinephrine, the number of beta-adrenergic receptors (beta-AR), both at the cardiac and the lymphocytic level, is reduced (down-regulation). Captopril, an ACE-inhibitor containing an SH group appears capable of resetting beta-AR when used in patients with heart failure. Our study was aimed at checking whether captopril exerts a direct effect upon the beta-AR, possibly through its SH group by disulphur binding with cysteine residues located at the binding sites for catecholamines., Methods: The study was carried out in vitro on human lymphocytes obtained from healthy volunteers: 10 males (mean age, 34 years; range, 25-45) and 10 females (mean age, 34 years; range 26-48). Lymphocytes were randomly divided in two groups of equal size. Group I were controls; in Group II cells were incubated with three different doses of captopril: 1, 10, and 100 microM. Control lymphocytes and those treated with 10 microM of captopril were exposed to 1 microM isoproterenol. The number of total and surface beta-AR, and the sequestration of beta-AR from isoproterenol under normoxic conditions and after 20 h of hypoxia were checked. Furthermore, the content of cAMP was assayed both in basal conditions and after stimulation with 10 microM and 100 microM isoproterenol and forskolin, respectively., Results: Total beta-AR: 1082 +/- 133 (controls) vs. 1174 +/- 94 (treatment with 1 microM captopril), vs. 1237 +/- 88 (10 microM captopril), vs. 1092 +/- 105 (100 microM captopril). Surface beta-AR: 84 +/- 4.41% (controls) vs. 90.5 +/- 2.1% (10 microM captopril). Basal cAMP: 1.21 +/- 0.4 (controls) vs. 1.23 +/- 0.5 pmol/10 cells (1 microM captopril), 1.05 +/- 0.6 pmol/10 cells (10 microM captopril), 1.15 +/- 0.4 pmol/10 cells (100 microM captopril). After 10 microM isoproterenol: controls 4.10 +/- 0.8 vs. 4.30 +/- 0.9 pmol/10 cells (1 microM captopril), 4.15 +/- 0.7 pmol/10 cells (10 microM captopril), 3.50 +/- 1.0 pmol/10 cells (100 microM captopril). After 100 microM forskolin: controls 13.2 +/- 3.1 vs. 11.2 +/- 3.1 pmol/10 cells (1 microM captopril), 13.1 +/- 4.2 pmol/10 cells (10 microM captopril), 12.6 +/- 2.9 pmol/10 cells (100 microM captopril). Neither of these differences were significant. Lymphocytic beta-AR exposed to hypoxia did not show any significant difference. Exposure to captopril did not cause any further alteration on beta-AR sequestration., Conclusions: Captopril does not seem to exert any direct action upon lymphocyte beta-AR from healthy volunteers. Moreover, captopril does not modify cAMP storage either in basal conditions or after stimulation with isoproterenol or forskolin. Therefore our data suggest that action of captopril on beta-AR is probably due to the inhibition of both systemic and tissue ACE-system.

Dopamine has been used for many years to treat patients with severe heart failure. It is not clear whether improvements of cardiac function may be due to a direct action on heart. This study was aimed to investigate the direct action of dopamine on failing heart. we chose male Wistar rats which had undergone uninephrectomy under ether anaesthesia to induce hypertension to result in heart failure. After 5 weeks the hearts were excised and perfused according to Langerdoff's technique. Heart rate, systolic and diastolic ventricular pressures, the derivative of the intraventricular pressure time ratio, and coronary flow were measured at baseline, at 2 and 5 min and then every 5 min during a 30-min period. Rat hearts were divided into 4 groups of 5 hearts: group 1, perfused without drug; group 2, perfused with dopamine at 4 micrograms/kg/min; group 3, perfused with dopamine at 8 micrograms/kg/min; group 4, perfused with dopamine at 8 micrograms/kg/min and with 100 nM I.C.I. 118.551 (beta 2-ant: beta-2 receptors antagonist) at the same time. Our results show that dopamine induced a negative inotropic effect and a reduction of coronary flow. Moreover, there was a significant chronotropic action even when dopamine was administered at high concentrations. So we found no positive dopamine effect on isolated failured hearts of rat. This might be explained by both alpha-1-induced vasoconstriction and the stimulation of alpha-1B receptors. We conclude that the favourable effects of dopamine in heart failure could be due to DA1 vasodilation rather than to a direct inotropic action on the heart.

Taking into account the possible regulatory influences of the beta-adrenergic system on lymphocyte proliferation as well as the proposed role of cyclic 3'-5'-adenosine monophosphate (cAMP) in the modulation of multidrug resistance (MDR) in tumour cells, we have tried to assess the status of the interactions between the beta-adrenergic system and a mouse lymphocytic leukemia, the P388, both as a doxorubicin-sensitive (P388) and -resistant (MDR) variant (P388/DXR). P388 showed a low total number of high affinity 125I-pindolol binding sites (340 +/- 33/cell, Kd 108 pM) when compared with normal splenocytes (1221 +/- 67 sites/cell, Kd 97 pM). The number of beta-adrenergic receptors was even lower in P388/DXR cells (230 +/- 41 sites/cell, Kd 101 pM). In addition, these receptors were subnormally expressed on the cell surface: only 26% and 52% of the total receptors were surface receptors in P388 and P388/DXR, respectively, whereas it was 87% in normal splenocytes. Isoproterenol slightly (less than 1-fold) stimulated cAMP accumulation in P388 and P388/DXR; the stimulation observed in splenocytes was 2.5-fold. In addition, the basal levels of cAMP appeared to be low (0.48 +/- 0.05 pmoles/10(6) cells in P388 and 0.71 +/- 0.08 pmoles/10(6) cells in P388/DXR; 3.47 +/- 0.28 pmoles/10(6) cells in splenocytes) in the two leukemias and they were only slightly (less than 2-fold) increased by forskolin, which otherwise stimulated about 15-fold cAMP accumulation in splenocytes; thus, P388 and P388/DXR were probably also defective in their adenylate cyclase activity. It can be concluded that, owing to multifactorial mechanisms, the lymphocytic leukemia P388, also as an MDR variant, is minimally sensitive to the direct influences of the beta-adrenergic system, probably including any effect of this system on drug-sensitivity.

In order to evaluate the possible effects of diagnostically employed ultrasounds on DNA turnover, 35 Wistar strain rats were subjected to an ultrasonic frequency band of 2.25 MHz for exposure times varying from 10 to 500 seconds. Upon administration of thymidine tritiate, it was observed that capacity to absorb the substance remained largely normal in those rats exposed for up to 40 seconds, but was diminished where longer exposure times were employed.