From the Centro di Fisiologia Clinica e Ipertensione, Cattedra di
Cardioangiologia Medica, Università di Milano, Ospedale Maggiore,
Milano; Cattedra di Medicina Interna (G.M.), Ospedale S. Gerardo, Monza; and
Divisione di Cardioriabilitazione (A.U.F.), Ospedale di Seregno, Az. Osp. Civ.
Vimercate (MI), Italy.
Correspondence to Dr Alberto U. Ferrari, Centro Fisiologia Clinica e Ipertensione, Via F. Sforza 35, 20122 Milano Italy. E-mail alberto.ferrari{at}unimi.it
Abstract—Conflicting evidence
exists on the possible impairment of tonic nitric oxide (NO)–mediated
vasodilation as a causative factor in the genesis of human as well as
experimental hypertension. We evaluated the tonic NO-dependent
vasodilation from the pressor response to NO synthesis inhibition by
NG-monomethyl-L-arginine
(L-NMMA) in 9 conscious, chronically instrumented spontaneously
hypertensive rats (SHR) at 12 weeks of age, ie, during the early
established hypertensive stage. Nine age-matched Wistar-Kyoto rats
(WKY) were used as controls. The pressor responses to L-NMMA (100
mg · kg-1 IV bolus plus 1.5 mg ·
kg-1 · min-1 infusion for 60 minutes)
as well as to non–NO-dependent pressor stimuli, namely, vasopressin
(2, 4, and 8 ng · kg-1) and
phenylephrine (0.5, 1, and 2 µg ·
kg-1) given as IV boluses, were assessed both under
control conditions and during suppression of autonomic reflexes by
hexamethonium (30 mg · kg-1 IV
bolus+1.5 mg · kg-1 · min-1
infusion). Rather than being reduced, the pressor responses to L-NMMA
were 39% and 71% larger in the control and areflexic conditions,
respectively, than those observed in WKY (both P<0.01).
A similar pattern was observed for the pressor responses to vasopressin
(+37% and +68% in the control and areflexic conditions, respectively;
both P<0.01) and phenylephrine, (+20% and
+52%; both P<0.05). Additional groups of 6-week-old
prehypertensive SHR (n=11) and age-matched WKY (n=11) were subjected to
an identical protocol: in these animals, the pressor responses to
L-NMMA were similar in each strain, as were the pressor responses to
vasopressin and phenylephrine in both control and areflexic
conditions. In conclusion, our observations indicate that during the
developmental phase of hypertension in the SHR model, namely, during
the prehypertensive as well as the early established hypertensive
stage, NO-dependent vasodilation is preserved (if not enhanced) so that
a putative impairment of this function provides no significant
pathogenic contribution to the onset of hypertension in this
experimental model.
© 1998 American Heart Association, Inc.
Scientific Contributions
Nitric Oxide–Dependent Vasodilation in Young Spontaneously Hypertensive Rats
Key Words: nitric oxide • rats, inbred SHR • vascular reactivity • L-NAME • hexamethonium
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