The electrical stimulation of the paraventricular nucleus (PVN) of the hypothalamus in anaesthetized rabbits elicited important cardiovascular responses which were mainly characterized by increases in arterial pressure, dP/dtmax, and of the indexes of myocardial oxygen consumption, rate-pressure product (from 34 +/- 2 to 40 +/- 2 mmHg.bpm.10(-3) and triple product (from 102 +/- 12 to 162 +/- 19 mmHg2.s-1.bpm.10(-6). The hemodynamic alterations induced by PVN stimulation were similar to those observed during physical effort and stressful situations. Intracerebroventricular (0.1, 0.3 and 1 microgram.kg-1) or intravenous administration (1, 3 and 10 mg.kg-1) of baclofen, a selective GABAB receptor agonist, induced a dose-related decrease in the peak values of dP/dtmax and of the indexes of myocardial oxygen consumption (rate-pressure and triple products) during the electrical PVN stimulation. After 1 microgram.kg-1 baclofen (i.c.v.), the peak value of the triple product during PVN stimulation was 101 +/- 21 as compared to 149 +/- 15 before treatment. At the 10 mg.kg-1 dose (i.v.), the triple product during stimulation only reached 90 +/- 20 vs. 150 +/- 20 before treatment. These results suggested that a type B GABAergic transmission system is involved in the modulation of central control of the cardiac function. Drugs modulating this system could therefore be designed to blunt the myocardial oxygen demand increases.

Verapamil compared with placebo improves long-term clinical outcome after PCI of native coronary arteries by reducing the need for TVR. This was caused by a reduction in the rate of high-grade restenosis.

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It has been shown in various mammal species that clonidine, a well known centrally acting hypotensive agent, acts through the activation of imidazoline receptors (IRs) in the nucleus reticularis lateralis (NRL) of the brainstem. Specific binding sites sensitive to imidazolines and insensitive to catecholamines have been detected in rat and bovine, as well as human brains. An endogenous ligand, other than catecholamines, should exist for these IRs. Such a ligand could play a role in the pathophysiology of human essential hypertension. Therefore, we developed two RIAs with polyclonal and monoclonal anticlonidine antibodies. These antibodies presented specificity spectra similar to that of the IRs: they bound imidazolines and not catecholamines at all. These RIAs were used to detect imidazoline-like immunoreactivity in the human serum. Immunoreactive substance was measured in 26 normotensive subjects' sera, and specificity of interaction between antibodies and sera was verified. None of the known endogenous substances tested so far were able to interact with the two antibodies. Immunoreactivity in 32 essential hypertensive patients' sera proved higher in -30% of cases. Values of immunoreactivity positively correlated with the mean arterial pressure values. This study demonstrates the existence of an "imidazoline-like" immunoreactive substance in the human serum with high levels in some hyper-

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