Vasodilatory effect of nicardipine and verapamil in the forearm of hypertensive as compared with normotensive man.

Abstract

1 The intent ofthis study was to determine whether or not increased calcium-influx-mediated vasoconstriction is a primary pathogenetic disturbance in essential hypertension. 2 Ten normotensive subjects (NT) (aged 45+12 years) and 23 patients with essential hypertension (EH) were studied. Twelve of the patients (aged 42 + 12 years) were classified as having mild EH and 11 patients (aged 49 +11 years) as having moderate EH. 3 Forearm blood flow and intra-arterial blood pressure were measured. Forearm vascular resistance (FVR) was calculated under basal conditions, during reperfusion following 10 min arterial occlusion, and after infusion into the brachial artery of sodium nitroprusside (0.15 and 0.6 ug min-' 100 ml-' tissue for 2 min each) and the calcium-influx inhibitors nicardipine (5 and 40 ug min-' 100 ml-' tissue for 1 min each) and verapamil (80 ug min-' 100 ml-' tissue for 1 min). 4 FVR after 10 min arterial occlusion was lower in mild EH than in moderate EH and still lower in NT. FVR was comparable in the three groups following infusion of maximal doses of sodium nitroprusside, nicardipine, and verapamil. 5 To allow for the vasodilator response to arterial occlusion, the decrease in FVR measured after each drug was divided by that obtained after arterial occlusion in each individual. The adjusted vasodilator response to nicardipine and verapamil, but not to sodium nitroprusside, was greater in moderate EH than in NT and mild EH. In the latter two groups the adjusted vasodilator responses were comparable. 6 Calcium-influx mediated vasoconstriction is thus enhanced in moderate (established) EH but not in mild EH and, therefore, is unlikely as a primary pathogenetic disturbance in essential hypertension.

Functional versus structural changes of forearm vascular resistance in hypertension.

“…This finding is in accordance with those of Hulthe'n et al , 12 who also found a greater reduction of the intra-arterially measured BP in hypertensive than in normotensive subjects during regional calcium entry blockade. By contrast, Folkow et al 4 observed only a small, insignificant decrease of mean BP in the experimental arm following arterial occlusion, which was comparable in both groups.…”

“…In the study of Hulthdn et al, 12 verapamil and nicardipine had a greater vasodilator effect than did arterial occlusion, while in our study the effect of ischemia proved to be stronger. The more intensive action of the arterial occlusion as compared with nifedipine infusion that was observed in our study was probably due to an additional vasodilator effect of local heating and handgrip exercise.…”

“…Forearm blood flow has been reported to be higher in patients with established hypertension than in normotensive subjects during infusion of the calcium entry blockers verapamil and nicardipine 12 and to show a greater increase under verapamil infusion. 15 These findings were interpreted as reflecting a functional disturbance with enhanced calcium influx-mediated vasoconstriction in the established phase of essential hypertension, as calcium entry blockers are believed to act by inhibiting the entry of calcium through poten- tial-operated channels.…”

“…Since resting blood flow values showed a wide variation (see Table 2), it is not surprising that the reports in the literature are conflicting. Forearm and skin blood flow rates in patients with established hypertension have been described to be increased, 10 ' 25 " 27 decreased, 7 or comparable to those of normotensive subjects, 12 ' 2829 and vascular resistance also has been reported to be increased, 7 ' 10 ' n -28 -30 -3I lowered, 26 or normal. 12 This wide variety of data is probably due to factors such as environmental conditions and emotional influences that are difficult to keep constant.…”

Resistance to blood flow at maximal vasodilation.

“…7 However, the overlap in our study was due to the fact that the blood pressure in the hypertensive patients as well as in the normotensive subjects declined substantially after maximal vasodilator maneuvers (by 17% and 12%, respectively) so that blood pressures of five out of 21 hypertensive patients fell into the normotensive range. This is in accordance with data by Hulth6n et al 8 The fall in blood pressure after vasodilator maneuvers obviously has been missed by Folkow et al, 9 because they did not measure the blood pressure directly in the experimental arm during vasodilation. It is clearly an advantage that we have recorded the blood pressure directly in our study, thereby detecting changes in blood pressure during vasodilator maneuvers.…”