Because apnea length during periodic breathing varies according to the preceding increase in ventilation and reduction in PaCO 2, differences in the cycle length of periodic breathing among patients with normal and impaired cardiac function might be explained by the influence of lung-to-carotid body circulatory delay, as reflected by lung-to-ear circulation time (LECT), on hyperpnea length rather than on apnea length. It was therefore hypothesized that circulatory delay is an important determinant of periodic-breathing hyperpnea length but not apnea length. To test this hypothesis, LECT, periodic-breathing cycle length, apnea length, and hyperpnea length were compared in 10 patients with idiopathic central sleep apnea (ICSA), whose cardiac function was normal, as opposed to 10 with Cheyne-Stokes respiration and central sleep apnea (CSR-CSA) in association with congestive heart failure (CHF). As compared with ICSA patients, cycle length was significantly longer in patients with CSR-CSA (37.3 +/- 3.0 s versus 59.0 +/- 4.9 s, p < 0.005). This difference was due to significantly longer hyperpnea length in the CSR-CSA patients (16.7 +/- 2.8 s versus 36.7 +/- 3.4 s, p < 0.001), since apnea length was similar in the two groups. In addition, LECT was longer in the CSR-CSA patients (24.3 +/- 2.0 s versus 10.3 +/- 1.0 s, p < 0.001), and correlated strongly with cycle length (r = 0.88, p < 0.001) and hyperpnea length (r = 0.90, p < 0.001) but not with apnea length. LECT correlated inversely with cardiac output (r = -0.72, p < 0.006), indicating that LECT is a valid measure of circulatory delay. Thus, circulatory delay is an important determinant of hyperpnea length but not of apnea length in patients with ICSA and CSR-CSA.

Animal studies suggest that some angiotensin coverting enzyme inhibitors augment endotheliumdependent vasorelaxation. We aimed to determine if captopril augments endothelium-dependent vasodilation in middle-aged hypertensive patients. By using strain-gauge plethysmography, forearm vasodilation evoked with intra-arteriaJ acetylchollne (4,8,16, and 24 /ig/min) or nitroprusside (0.2, 0.4, 0.8, and 1.2 /tg/min) was examined before and after captopril administration (25 mg per os). Before captopril, forearm vasodilation with acetylcholine was less in hypertensive patients (n=12) than in age-matched (n=7) or young (n=7) normotensive subjects, but forearm vasodilation with nitroprusside did not differ among the three groups. Captopril improved forearm vasodilation in hypertensive patients (n=l) with acetylcholine but nitroprusside did not In contrast, nifedipine (10 mg per os) did not alter forearm vasodilation with acetylcholine or nitroprusside in hypertensive patients (n=5). The decreases in mean blood pressure caused by captopril and nifedipine in hypertensive subjects were comparable. Captopril did not alter forearm vasodilation with acetylcholine or nitroprusside in young normotensive subjects (n=7). These results suggest that captopril in hypertensive patients may acutely improve impaired endothelium-dependent forearm vasodilation that does not result from reduction in blood pressure per se. I n experimental animals, chronic hypertension is associated with attenuated endothelium-dependent relaxation to acetylcholine (ACh). 1 -4 The impairment of endothelium-dependent relaxation in hypertension is closely correlated with the degree of hypertension and may improve after chronic antihypertensive therapy. -5 Recent studies in humans also have shown that endothelium-dependent forearm vasodilation to ACh is impaired in patients with essential hypertension. 6 -7 A recent study has suggested that lisinopril, an angiotensin converting enzyme inhibitor, increased compliance of the in situ isolated carotid arteries in the presence of the intact endothelium but did not alter it after endothelium removal in Wistar-Kyoto and spontaneously hypertensive rats.

Our results suggest that L-NMMA decreased FBF after exercise largely by decreasing resting FBF. These results suggest that NO may not play a significant role in exercise-induced metabolic arteriolar vasodilation in the forearm of healthy humans.

Our results suggest that defective endothelial function may contribute to impaired ischemic vasodilator capacity in HF.

Arginine vasopressin (AVP) causes biphasic changes in vascular resistance in human forearms; vasoconstriction at lower doses and vasodilation at higher doses. Vasoconstriction is mediated by the V1 receptor. However, the mechanism of AVP-induced vasodilation is not known. We investigated whether AVP-induced vasodilation is mediated by nitric oxide (NO) in human forearms by examining the effects of L-arginine (a precursor of NO) and NG-monomethyl-L-arginine (L-NMMA, a blocker of NO synthase) on AVP-induced vasodilation. AVP was infused intraarterially at doses of0.05, 0.1, 0.2, 0.5, and 1.0 ng/kg per min (n = 8). The lower doses of AVP (< 0.1 ng/kg per min) increased, whereas the higher doses of AVP (> 0.5 ng/ kg per min) decreased forearm vascular resistance (FVR) (P < 0.01). Intraarterially infused L-arginine at 10 mg/min did not alter arterial pressure, baseline FVR, or heart rate. L-arginine did not alter the magnitude of AVP-induced vasoconstriction at the lower doses, but L-arginine augmented the magnitude of AVP-induced vasodilation at doses of 0.2 (P < 0.05), 0.5 (P < 0.01), and 1.0 (P < 0.05) ng/kg per min. In another group (n = 6), intraarterially infused L-NMMA (4 ,gmol/min for 5 min) increased baseline FVR without systemic effects, and inhibited acetylcholine-induced vasodilation (P < 0.01). L-NMMA at this dose inhibited AVP-induced vasodilation (P < 0.01 ) but did not affect vasoconstriction. L-arginine reversed the inhibitory effect of L-NMMA. Our results suggest that the vasodilatory effect of AVP may be mediated by NO in human forearms. (J. Clin. Invest. 1993. 92:1483-1490