The vasoconstrictor effect, the binding, and the response of inositol phosphates to endothelin-1 (ET-1) were investigated in blood vessels of deoxycorticosterone acetate (DOCA) -salt hypertensive rats within 2 weeks of development of hypertension and in uninephrectomized control rats. In DOCA-salt and uninephrectomized rats, plasma levels of endothelin were similar (1.2±0.1 fmol/ml). Thoracic aorta and mesenteric artery rings devoid of endothelium presented significantly decreased responses to increasing concentrations of ET-1. Binding of ET-1 to mesenteric artery membranes was significantly lower in DOCA-salt rats (106±22 fmol/mg protein) than in uninephrectomized rats (172 ±19 fmol/mg protein, p< 0.05), whereas affinity was similar. Phosphoinositide metabolism was examined in aorta and mesenteric arteries after incubation with The endothelium synthesizes and releases paracrine hormones that regulate the contraction and physiology of vascular smooth muscle cells. 4 In addition to the well-described vasorelaxant factors (i.e., endo-

1 Caspases, key enzymes in the apoptosis pathway, have been detected in the brain of HD patients and in animal models of the disease. In the present study, we investigated the neuroprotective properties of a new, reversible, caspase-3-specific inhibitor,, in a rat malonate model of HD. 2 Pharmacokinetic and autoradiography studies after intrastriatal (i.str.) injection of 1.5 nmol of M826 or its tritiated analogue [ 3 H]M826 indicated that the compound diffused within the entire striatum. The elimination half-life (T 1/2 ) of M826 in the rat striatum was 3 h. 3 I.str. injection of 1.5 nmol of M826 10 min after malonate infusion induced a significant reduction (66%) in the number of neurones expressing active caspase-3 in the ipsilateral striatum. 4 Inhibition of active caspase-3 translated into a significant but moderate reduction (39%) of the lesion volume, and of cell death (24%), 24 h after injury. The efficacy of M826 at inhibiting cell death was comparable to that of the noncompetitive NMDA receptor antagonist MK801. 5 These data provide in vivo proof-of-concept of the neuroprotective effects of reversible caspase-3 inhibitors in a model of malonate-induced striatal injury in the adult rat.

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The effect of a synthetic atrial natriuretic peptide (atriopeptin III) on blood pressure, heart rate, and hematocrit was investigated in conscious, nephrectomized (n = 6), and sham-operated (n = 6) rats. Atriopeptin III infusion (1 microgram/min iv for 30 min) decreased mean blood pressure to a similar extent in nephrectomized [from 122 +/- 5 to 108 +/- 3 (SE) mmHg; P less than 0.01] and in sham-operated rats (from 124 +/- 4 to 103 +/- 2 mmHg; P less than 0.01), whereas it had no significant effect on heart rate. Hematocrit rose similarly in nephrectomized (from 45 +/- 1 to 49 +/- 1%; P less than 0.01) and in sham-operated rats (from 46 +/- 1 to 50 +/- 1%; P less than 0.001). Infusion of the vehicle of atriopeptin III to nephrectomized rats (n = 7) did not change any of these parameters. Plasma volume and red cell mass of nephrectomized rats infused with atriopeptin III was measured by use of radiolabeled albumin and erythrocytes, respectively. A plasma volume contraction of approximately 10% (P less than 0.01) was observed, whereas red cell mass did not change. In an additional group of nephrectomized rats (n = 6), Na nitroprusside was infused intravenously at a rate of 2 micrograms/min for 30 min. Na nitroprusside reduced mean blood pressure from 127 +/- 4 to 106 +/- 3 mmHg (P less than 0.001), but hematocrit remained unchanged (46 +/- 1% before vs. 45 +/- 1% after infusion). In four anesthetized rats with both kidneys and the spleen removed atriopeptin III still raised the hematocrit.(ABSTRACT TRUNCATED AT 250 WORDS)

A new system was developed in our laboratory to continuously monitor intra-arterial pressure, heart rate, and sympathetic nerve activity in unanesthetized rats. The animals were prepared 24 h before the start of the experiments. Sympathoneural traffic was measured at the level of splanchnic nerve. The amplitude of the spikes recorded at this level was utilized to express sympathetic nerve activity. The amplitude of the residual electroneurogram signal present 30 min after the rats were killed was 32 +/- 2 mV (mean +/- SE; n = 11). For analysis, these background values were subtracted from values determined in vivo. The nerve we studied contains postganglionic fibers, since electrical activity decreased in response to ganglionic blockade with pentolinium (1.25 mg/min iv for 4 min). The amplitude of spikes fell by 43 +/- 4% (n = 4). Sympathetic nerve activity was highly reproducible at a 24-h interval (104 +/- 26 vs. 111 +/- 27 mV for the amplitude of spikes; n = 11). Dose-response curves to the alpha 1-stimulant methoxamine and to bradykinin were established in four rats. The increase in blood pressure induced by methoxamine caused a dose-dependent fall in sympathetic nerve activity, whereas the blood pressure reduction resulting from bradykinin was associated with a dose-dependent activation of sympathetic drive. These data therefore indicate that it is possible with out system to accurately measure sympathetic nerve activity in the awake rat, together with intra-arterial pressure and heart rate.