Proteoglycan production by vascular smooth muscle cells from resistance arteries of hypertensive rats.

Extracellular matrix (ECM) modifications in the vascular wall contribute to the narrowing of arteries in hypertension. Because direct evidence for the role of proteoglycans (PGs) in the pathological process of resistance-sized arteries has not already been demonstrated, we examined the effect of growth factors on secreted and membrane-bound PG synthesis by cultured mesenteric vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and Wistar rats. After 48 hours of stimulation with angiotensin II (Ang II), platelet-derived growth factor (PDGF-BB), and 10% fetal calf serum (FCS) or 0.1% FCS as control, PG synthesis (in dpm/ng DNA) was evaluated in the medium (M-ECM) and in the cell layer (P-ECM) by a double-isotopic label method with both [(3)H]-glucosamine and [(35)S]-sodium sulfate, which are incorporated into all complex carbohydrates or only into sulfated disaccharides, respectively. VSMC from SHR displayed a significantly lower level of synthesis of M-ECM [(3)H]-PGs than those of Wistar rats in all the experimental groups, including the control group (0. 1% FCS), but no differences in M-ECM [(35)S] uptake were found in any case. In the P-ECM, Ang II was the only factor that produced a lesser effect on [(3)H]-glucosamine and a greater effect on [(35)S]-sodium sulfate uptakes in VSMC from SHR than from Wistar rats. The most prominent change seen in VSMC from SHR was an increased sulfation, assessed by [(35)S]/[(3)H] ratio, in nonstimulated cells and in response to 10% FCS and Ang II but not to PDGF-BB compared with VSMC from Wistar rats. These data indicate the existence of changes in PG modulation in the resistance vessels of SHR, which suggests that PGs may contribute to the development of structural and functional modifications in hypertensive states.

Magnesium: effects on reperfusion arrhythmias and membrane potential in isolated rat hearts.

The effects of Mg2+ concentration (Mg2+o, 0, 1.2, 2.4, and 4.8 mM) on the incidence of reperfusion arrhythmias and on the cellular electrical activity were studied in spontaneously beating rat hearts. The surface electrogram and the membrane potential were recorded in control conditions, during 10 min of regional ischemia (ligature of the left anterior descending coronary artery), and on reflow. Changes in Mg2+o did not alter action potential morphology but the depolarization induced by ischemia decreased with increasing Mg2+o. In hearts perfused with Mg2+ free solution or 1.2 mM subthreshold delayed afterdepolarizations (DADs) were often detected during ischemia. Moreover, DADs could be identified as initial events in the production of extrabeats or tachycardia appearing on reperfusion under these conditions. Chaotic electrical activity during fibrillation precluded the observation of DADs. The overall incidence (100%) and severity of ventricular tachyarrhythmias (80% tachycardia and fibrillation) was similar in both groups. At high Mg2+o, subthreshold DADs were occasionally observed during ischemia and often on reperfusion where they did not lead to the development of overt arrhythmias. Consequently, the incidence, severity, and duration of arrhythmic episodes on reflow was markedly reduced. Raising Mg2+ only on reperfusion did not prevent the development of arrhythmias, whose morphology in the intracellular recordings was similar to that found in hearts perfused without Mg2+ or with 1.2 mM. The recovery of sinus rhythm after 10 min of reperfusion was linearly related to Mg2+o. Our data strengthen the view that reperfusion arrhythmias belong to the Ca2+ mediated non reentrant type and suggest that Mg2+ counteracts these arrhythmias by depressing cytosolic Ca2+ oscillations. Besides, it appears that raising Mg2+o reduces ischemic K+o accumulation. The resulting changes in resting potential could contribute to lower DADs amplitude and thus decrease the arrhythmogenic potential of the Ca2+i oscillations induced by reperfusion.

Effect of beta adrenoreceptor blocking drugs on the responses of isolated rat mesenteric arteries.

The effect of several beta-blockers on the vasoactive effect of several substances was studied on the perfused isolated rat mesenteric vessels. The agonists were tested while the beta-blocker was infused; the effects were compared in the same experiment with those observed in a control period in which the agonists were injected without simultaneous infusion of beta-blocker. l-propranolol, infused at three different doses, did not modify the vascular effect of either angiotensin II (AII) or vasopressin (VP). On the other hand, the constrictor effect of epinephrine (E) and norepinephrine (NE) was significantly reduced. Timolol, but not sotalol, showed the same results. d-propranolol produced the same effect as l-propranolol. A high dose of l-propranolol did not protect alpha adrenoceptors of blockade induced by phentolamine.

Effect of beta adrenoreceptor blocking drugs on the responses of isolated rat mesenteric arteries.

The effect of several beta-blockers on the vasoactive effect of several substances was studied on the perfused isolated rat mesenteric vessels. The agonists were tested while the beta-blocker was infused; the effects were compared in the same experiment with those observed in a control period in which the agonists were injected without simultaneous infusion of beta-blocker. l-propranolol, infused at three different doses, did not modify the vascular effect of either angiotensin II (AII) or vasopressin (VP). On the other hand, the constrictor effect of epinephrine (E) and norepinephrine (NE) was significantly reduced. Timolol, but not sotalol, showed the same results. d-propranolol produced the same effect as l-propranolol. A high dose of l-propranolol did not protect alpha adrenoceptors of blockade induced by phentolamine.