1 Nitric oxide (NO) has been suggested as the mediator of the vascular response to bradykinin. In the present study, we found that NO did not mediate the hypotensive response to bradykinin. In addition, the significance of kininase II in terminating a kinin-induced hypotension and the role of the adrenergic system in compensating for the acute fall in blood pressure (BP) was established. 2 In normal rats, the NO-synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) induced a rise in basal BP (ABP =40±6 mmHg, P<0.0014) which was not altered by pretreatment with phentolamine (ABP = 50 ± 6 mmHg, NS). L-NAME did not attenuate the acute fall in BP in response to bradykinin (3-30 1gkg-') or kallikrein (6-300 1gkg-'). However, a significant decrease was observed in the duration of the hypotensive response (P<0.027). This shorter duration was not observed after pretreatment with phentolamine in addition to L-NAME. Phentolamine alone prolonged the hypotensive response to bradykinin (P<0.04). These experiments confirm the role of NO-formation as a hypotensive component in BP homeostasis but not the role of NO as a mediator in kinin-induced hypotension. It further shows that the continuous NO-release also impedes the compensatory adrenergic hypertensive response following the acute fall in BP induced by bradykinin. 3 The hypertensive respose to intravenously administered phenylephrine was found to be unchanged by preadministration of L-NAME (NS) thus showing that L-NAME did not change the sensitivity to the adrenergic response. In a separate protocol on L-NAME-treated rats we found no difference in heart rate (NS) during the recovery period following bradykinin before as compared to after administration of phentolamine. It was therefore concluded that the observed alterations in the duration of the hypotensive response were most probably due to changes in peripheral vascular resistance. 4 To confirm further that NO is not a mediator in kinin-induced hypotension, we used an experimental model where the response to bradykinin was profonged by preventing kinin degradation by kininase II-converting enzyme inhibitor (CEI). To produce a hypotensive response purely dependent on kinin, the studies were performed after removal of the renin-angiotensin system by nephrectomy (Nx). In this model, bradykinin (6 pg kg-', i.v.) induced a prolonged hypotensive response. Pretreatment with L-NAME did not alter the magnitude or the progression of the hypotensive response to bradykinin, thus confirming that NO was not a mediator in BK-induced hypotension. 5 To study the mechanisms involved in terminating the hypotensive response to bradykinin, the results from the Nx CEI-treated rats were compared with Nx animals not treated with CEL. In the latter group, bradykinin induced a short hypotensive response, i.e. 0.5 ± 0.1 min as compared to the 17 ± 1 min after CEI (P<0.003). After kininase II-inhibition (and L-NAME), BP recovery was totally dependent on the adrenergic system, since phentolamine prevented a recovery in BP during the exper...

The sensitivity of prenatal ultrasound in diagnosing the congenital malformations under study in a low risk population was 19% at 17-18th week of gestation and 36% throughout the pregnancy. Prenatal diagnosis altered management of labor, but caused no improvement in neonatal outcome.

We studied the role of nitric oxide and adrenergic activation in the blood pressure (BP) response to exogenous bradykinin in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Rats were pretreated with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the alpha-adrenergic receptor antagonist phentolamine together with L-NAME, or phentolamine alone. Sham-injected rats were used as controls. All rats subsequently received bradykinin (3, 6, and 30 micrograms/kg i.v.). Bradykinin induced a concentration-dependent fall in BP in both WKY and SHR (P < .0005). The change in BP was greater in SHR than WKY (P < .0001). BP before bradykinin administration was elevated in the L-NAME group in both strains. In WKY, L-NAME or L-NAME plus phentolamine did not alter the delta BP concentration-response curve to bradykinin (P = NS), whereas in SHR, the delta BP concentration-response curve was attenuated (P < .0048). The attenuation was observed for the two lower bradykinin doses (P < .0005) but not the highest. In SHR, phentolamine alone reduced BP before bradykinin to the same level as in WKY controls, and its delta BP concentration-response curve was not different from that of the normotensive controls or L-NAME and L-NAME plus phentolamine SHR groups. No difference was observed in the duration of the hypotensive response in SHR compared with WKY. The present results confirm that in normotensive rats, the hypotensive effect of bradykinin was mediated by an unknown mechanism other than through the release of nitric oxide. However, in SHR, this mechanism was amplified by additional activation of nitric oxide synthesis. This bradykinin-activated nitric oxide production may be a pressure-induced mechanism to counteract the hypertensive condition.

A small volume centre may achieve satisfactory results for BA patients. The study has, however, identified factors that may further improve results; earlier referral, optimizing diagnostic work-up and establishing one dedicated surgical team.

1 The role of endogenous bradykinin in mean arterial blood pressure (BP) homeostasis was studied in spontaneously hypertensive (SHR) and normotensive (WKY) rats by the use of a bradykinin B2-receptor antagonist (BKant; Hoe 140, 11.6 pg kg-') and converting enzyme (kininase II) inhibitor (captopril, 10 mg). To obtain a response to captopril that was induced through inhibition of kinin-degradation only and not through inhibition of angiotensin II-formation, the studies were performed on binephrectomized male rats to eliminate the renin-angiotensin system. 2 The role of the nitric oxide (NO) and the adrenergic systems were evaluated by the use of NOsynthase inhibitor (L-NAME, 0.3 g kg-') and phentolamine (2 mg kg-'), respectively. 3 The rats were anaesthetized and pretreated with two injections of vehicle (PBS) or drugs spaced 5 min apart: PBS + PBS; BKant + PBS; PBS + L-NAME; BKant + L-NAME; or phentolamine + L-NAME. All rats were given captopril 15 min later. Time-control groups were treated with L-NAME but not captopril. 4 In WKY rats, captopril did not significantly alter BP in any of the groups. In the SHR-PBS + PBS group, on the other hand, captopril induced an immediate fall in BP (ABP = -23 + 4 mmHg, P< 0.0017) which was completely blocked by BKant (ABP=2+2 mmHg) (P<0.0011). L-NAME did not significantly alter the immediate hypotensive response to captopril but disclosed a later hypertensive reaction. In L-NAME + BKant-treated rats, both the hypotensive response and the late hypertension was abolished. In rats treated with phentolamine + L-NAME, the immediate fall in BP was not different from the controls whereas the late hypertension was absent. 5 BKant itself had no effect on basal BP in either WKY or SHR even when a 10 times higher dose was tested in a separate set of experiments. This was true also for conscious, nonnephrectomized SHR rats. 6 It was concluded that endogenous production of bradykinin was demonstrable through kininase IIinhibition in hypertensive but not in normotensive rats. However, this endogenous bradykinin did not play a role in basal BP homeostasis. The captopril-induced hypotension depended on kinin but, under the present conditions, not on NO as a mediator. The fall in BP induced a compensatory adrenergic hypertensive response which was revealed when the continuous NO-synthesis was blocked by L-NAME.