Lack of NO Formation Is Involved in the Vasodilative Response to Contrast Media.

Intravascular injection of angiographic contrast media results in peripheral vasodilation and hypotension. The mechanisms underlying these hemodynamic changes are not entirely clear. We hypothesized that increased formation of nitric oxide (NO) could be involved in the vasodilatory response to contrast media. To address this assumption we have investigated whether N(G)-monomethyl-L-arginine (L-NMMA, 200 mg/kg) and N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg), two specific NO formation inhibitors, can abolish the hypotensive response to intravascular injection of isopaque amin (1 g/kg), a contrast medium, as well as bradykinin (10 µg/kg), a NO-dependent vasodilator, in anaesthetized normotensive rats. In rats before pretreatment with L-NMMA and L-NAME, the absolute values of the average fall in mean arterial pressure (MAP) induced by intravascular injection of isopaque amin and bradykinin were 21.3 +/- 2.1 and 37.2 +/- 4.4 mmHg, respectively. Pretreatment with L-NMMA and L-NAME failed to affect the hypotensive response to isopaque amin; by administering isopaque amin in rats pretreated with L-NMMA and L-NAME the absolute values of the average fall in MAP were 25.6 +/- 4.9 and 23.4 +/- 3.9 mmHg, respectively, similar to the average fall in MAP before treatment with NO formation inhibitors. In contrast, the hypotensive response to bradykinin was significantly inhibited; by administering bradykinin in rats pretreated by L-NMMA and L-NAME, the absolute values of the average fall in MAP were 10.2 +/- 2.8 and 7.2 +/- 2.2 mmHg, respectively, much less than the average fall in MAP before treatment with NO formation inhibitors. We conclude that intravascular injection of isopaque amin causes reduction in systemic arterial pressure. However, this vasodilative effect seems unrelated majorly to augmented endothelium-derived NO formation.

Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits.

1. The in vivo antiatherogenic activity of the calcium antagonist, lacidipine, was investigated in two different types of atherosclerotic lesions (proliferative and fatty lesions) induced in rabbits. 2. The proliferative lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty lesions were induced by cholesterol feeding. Cholesterol (1%) and lacidipine (1, 3, and 10 mg kg-1) were given daily mixed with standard diet for 8 weeks to White New Zealand rabbits. The intimal hyperplasia (proliferative lesion) was induced 6 weeks after dietary and drug treatment started. 3. The neointimal formation was determined by measuring cross sectional thickness of intimal (I) and medial (M) tissue of fixed arteries. In untreated animals (n = 5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries with no collar (sham) showed an I/M tissue ratio of 0.03 +/- 0.02, whereas in the carotid with collar the ratio was 0.62 +/- 0.12. In lacidipine-treated animals a significant and dose-dependent effect on proliferative lesions at all three doses tested, was observed. I/M ratios were 0.47 +/- 0.02, 0.40 +/- 0.09, 0.32 +/- 0.02 for doses 1, 3, and 10 mg kg-1 day-1, respectively (P < 0.05). 4. The fatty lesion extent was significantly reduced by lacidipine at the 10 mg kg-1 day-1 dose, although a trend was also observed with lower dosage. 5. These results suggest a direct antiatherosclerotic effect of lacidipine, independent of modulation of risk factors such as hypercholesterolaemia and/or hypertension. Furthermore, the proliferative lesions are apparently more sensitive to lacidipine than are lipid-rich lesions.

Effects of treatment with verapamil SR and captopril on the lipid profile of hypertensive patients.

The potential beneficial effects of antihypertensive drugs on cardiovascular morbidity and mortality may be compromised by their adverse effects on serum lipid levels. In our study we compared verapamil and captopril and evaluated their effects on blood pressure and on serum lipid and lipoprotein levels, with particular attention to lipoprotein(a) [Lp(a)]. 20 hypertensive patients were treated with sustained release verapamil 240mg once daily or captopril 25mg twice daily for 3 months in a double-blind randomised study. Diastolic blood pressure was reduced from 100 +/- 3mm Hg to 87 +/- 6mm Hg (p < 0.01) and from 100 +/- 5mm Hg to 92 +/- 7mm Hg (p < 0.05) in the verapamil and captopril groups, respectively. Small but significant changes in serum lipid levels were noted: total cholesterol was reduced from 6 to 5.8 mmol/L (verapamil) and from 6.1 to 5.9 mmol/L (captopril); low density lipoprotein (LDL) cholesterol was reduced from 4 to 3.8 mmol/L (verapamil) and from 4.2 to 3.9 mmol/L (captopril); apolipoprotein C-III was reduced from 0.3 +/- 0.07 to 0.2 +/- 0.06 mmol/L (9.7 +/- 2.5 to 9.2 +/- 2.3 mg/dl) [verapamil] and from 0.2 +/- 0.1 to 0.2 +/- 0.09 mmol/L (9.1 +/- 3.7 to 8.3 +/- 3.4 mg/dl) [captopril]; apolipoprotein A-II increased only with verapamil (p < 0.02). Lp(a) levels showed only minor changes in individual patients. In conclusion, in our study verapamil and captopril were effective antihypertensive agents and did not adversely effect the lipid profile.

Serum lipids and apolipoproteins in patients with essential hypertension.

Fifty hypertensive untreated outpatients (34 women, 16 men), with stage I and II essential hypertension, were studied in comparison to 50 age- and sex-matched controls with similar life-styles. Total cholesterol triglycerides, LDL-cholesterol, VLDL-cholesterol, and HDL-cholesterol were measured by enzymatic methods, and apolipoproteins AI, AII, B, CII, CIII and E by RID. The results showed significant differences between hypertensives and controls respectively in triglycerides (135.2 +/- 73.9 versus 90.2 +/- 33.8, P less than 0.01) and VLDL cholesterol (26.7 +/- 14.8 versus 17.7 +/- 6.6, P less than 0.01) while no significant differences were observed in total, LDL and HDL cholesterol. Significant differences between the two groups were also observed in apolipoproteins, particularly in apo AI (130.0 +/- 28.2 versus 144.9 +/- 27.9, P less than 0.05), apo AII (32.9 +/- 10.2 versus 39.6 +/- 11.4, P less than 0.01), apo CII (4.0 +/- 2.6 versus 5.4 +/- 2.9, P less than 0.05) and apo E (5.0 +/- 1.8 versus 4.3 +/- 1.8, P less than 0.05), while no significant differences were observed in apo B and CIII values. The results suggest that in untreated hypertensive patients alterations in the apolipoproteins profile are present which, in part, may be responsible for the elevated incidence of cardiovascular disease, independently from the blood pressure values.

Platelet activation indices and apolipoproteins in hypertensive patients.

We have studied the platelet activation indices beta-thromboglobulin (beta-TG and platelet factor 4(PF4), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and apolipoprotein (A1, A2, B, C2, C3, E) profiles of 22 untreated essential hypertensive subjects (WHO stages 1 and 2) and 22 controls, to see if there might be some causal relationship between lipoprotein abnormalities and greater platelet activation. The results showed the patients had both greater platelet activation than the controls, as demonstrated by higher plasma beta-TG levels (P less than 0.01) and lower apolipoprotein A2 levels (P less than 0.05). However there were no significant correlations between the platelet activation indices and the plasma levels of apolipoproteins, lipoproteins or lipids in either group.