In vivo inhibition of nitric oxide synthesis does not depend on renin-angiotensin system activation

The role of heart rate in the modulation of the decreased cardiac output induced by acute nitric oxide synthesis inhibition in anaesthetized dogs

“…Although L-NAME has been reported to present effects independent of NO inhibition (Buxton et al, 1993;Hellmich & Gyermek, 1997), it markedly inhibits the brain NO synthase activity in the same range of doses used in this study (Zappellini et al, 1996a). Furthermore, the inactive enantiomer D-NAME fails to affect all the haemodynamic parameters here examined (Zappellini et al, 1996b) thus confirming that haemodynamic changes by L-NAME are in fact due to NO synthesis inhibition.…”

“…The acute administration of nitric oxide (NO) synthesis inhibitors such as N v -nitro-L-arginine methyl ester (L-NAME) to a number of animal species leads to a marked hypertension due primarily to extensive vasoconstriction and hence increased systemic vascular resistance (Moncada, Palmer & Higgs, 1991). Hypertension induced by L-NAME may also be accompanied by decreases in both heart rate (bradycardia) and cardiac output (Gardiner, Compton, Kemp & Bennett, 1990;Fozard & Part, 1991;Huckstorf, Zanzinger, Fink & Bassenge, 1994;Herity, Allen, Silke & Adgey, 1994;Zappellini, Moreno, Antunes & de Nucci, 1996a;Zappellini, Teixeira, Muscara, Zatz, Antunes & de Nucci 1996b). The mechanisms underlying the decreased cardiac output by L-NAME are still controversial.…”

Aminoguanidine produces beneficial haemodynamic effects in a canine model of acute pulmonary thromboembolism

“…The most probable reason for this lack of effect is that baseline NOx levels remained after l ‐NAME‐induced NOS inhibition and/or the long half‐time of nitrate in the circulation. Moreover, the dose of l ‐NAME used in the present study does not completely inhibit NOS activity (Zappellini et al. 1996).…”

“…2001); (5) NAME + Emb group ( n = 4), which received the same l ‐NAME infusions as described above and were embolized 30 min after the l ‐NAME infusions were started; (6) AG + Emb group ( n = 7), which received the same aminoguanidine infusions as described above and were embolized 30 min after the aminoguanidine infusions started. The doses of l ‐NAME and aminoguanidine used in the present study were based on previous studies showing that these doses produced marked inhibition of NOS activity (by more than 60%) (Zappellini et al. 1996, Faro et al.…”

“…This model of APT is very similar to that previously reported (Lee et al 2001); (5) NAME + Emb group (n = 4), which received the same l-NAME infusions as described above and were embolized 30 min after the l-NAME infusions were started; (6) AG + Emb group (n = 7), which received the same aminoguanidine infusions as described above and were embolized 30 min after the aminoguanidine infusions started. The doses of l-NAME and aminoguanidine used in the present study were based on previous studies showing that these doses produced marked inhibition of NOS activity (by more than 60%) (Zappellini et al 1996, Faro et al 1999) and significant haemodynamic effects (Evgenov et al 2000) respectively. Corresponding to the lung embolization with the clots produced from 5 mL kg )1 blood, the dogs in the Sham, NAME and AG groups received a saline 5 mL injection via the cannula placed in the right atrium.…”