Interactions between angiotensin II and nitric oxide during exercise in normal and heart failure rats

J. David Symons, Charles L Stebbins, Timothy I. Musch

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

We hypothesized that nitric oxide (NO) opposes ANG II-induced increases in arterial pressure and reductions in renal, splanchnic, and skeletal muscle vascular conductance during dynamic exercise in normal and heart failure rats. Regional blood flow and vascular conductance were measured during treadmill running before (unblocked exercise) and after 1) ANG II AT1- receptor blockade (losartan, 20 mg/kg ia), 2) NO synthase (NOS) inhibition [N(G)-nitro-L-arginine methyl ester (L-NAME); 10 mg/kg ia], or 3) ANG II AT1-receptor blockade + NOS inhibition (combined blockade). Renal conductance during unblocked exercise (4.79 ± 0.31 ml · 100 g-1 · min- 1 · mmHg-1) was increased after ANG II AT1-receptor blockade (6.53 ± 0.51 ml · 100 g-1 · min-1 · mmHg-1) and decreased by NOS inhibition (2.12 ± 0.20 ml · 100 g-1 · min-1 · mmHg-1) and combined inhibition (3.96 ± 0.57 ml · 100 g-1 · min-1 · mmHg-1; all P < 0.05 vs. unblocked). In heart failure rats, renal conductance during unblocked exercise (5.50 ± 0.66 ml · 100 g-1 · min-1 · mmHg-1) was increased by ANG II AT1-receptor blockade (8.48 ± 0.83 ml · 100 g-1 · min-1 · mmHg-1) and decreased by NOS inhibition (2.68 ± 0.22 ml-1 · 100 g-1 · min-1 · mmHg-1; both P < 0.05 vs. unblocked), but it was unaltered during combined inhibition (4.65 ± 0.51 ml · 100 g-1 · min-1 · mmHg- 1). Because our findings during combined blockade could be predicted from the independent actions of NO and ANG II, no interaction was apparent between these two substances in control or heart failure animals. In skeletal muscle, L-NAME-induced reductions in conductance, compared with unblocked exercise (P < 0.05), were abolished during combined inhibition in heart failure but not in control rats. These observations suggest that ANG II causes vasoconstriction in skeletal muscle that is masked by NO-evoked dilation in animals with heart failure. Because reductions in vascular conductance between unblocked exercise and combined inhibition were less than would be predicted from the independent actions of NO and ANG II, an interaction exists between these two substances in heart failure rats. L-NAME-induced increases in arterial pressure during treadmill running were attenuated (P < 0.05) similarly in both groups by combined inhibition. These findings indicate that NO opposes ANG II-induced increases in arterial pressure and in renal and skeletal muscle resistance during dynamic exercise.

Original languageEnglish (US)
Pages (from-to)574-581
Number of pages8
JournalJournal of Applied Physiology
Volume87
Issue number2
StatePublished - 1999

Fingerprint

Angiotensin II
Nitric Oxide
Heart Failure
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Skeletal Muscle
Blood Vessels
Kidney
Arterial Pressure
Running
Losartan
Viscera
Regional Blood Flow
Vasoconstriction
Dilatation

Keywords

  • Losartan
  • N(G)-intro- L-arginine methyl ester
  • Regional blood flow
  • Vascular conductance
  • Vascular resistance

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Interactions between angiotensin II and nitric oxide during exercise in normal and heart failure rats. / Symons, J. David; Stebbins, Charles L; Musch, Timothy I.

In: Journal of Applied Physiology, Vol. 87, No. 2, 1999, p. 574-581.

Research output: Contribution to journalArticle

Symons, J. David ; Stebbins, Charles L ; Musch, Timothy I. / Interactions between angiotensin II and nitric oxide during exercise in normal and heart failure rats. In: Journal of Applied Physiology. 1999 ; Vol. 87, No. 2. pp. 574-581.
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N2 - We hypothesized that nitric oxide (NO) opposes ANG II-induced increases in arterial pressure and reductions in renal, splanchnic, and skeletal muscle vascular conductance during dynamic exercise in normal and heart failure rats. Regional blood flow and vascular conductance were measured during treadmill running before (unblocked exercise) and after 1) ANG II AT1- receptor blockade (losartan, 20 mg/kg ia), 2) NO synthase (NOS) inhibition [N(G)-nitro-L-arginine methyl ester (L-NAME); 10 mg/kg ia], or 3) ANG II AT1-receptor blockade + NOS inhibition (combined blockade). Renal conductance during unblocked exercise (4.79 ± 0.31 ml · 100 g-1 · min- 1 · mmHg-1) was increased after ANG II AT1-receptor blockade (6.53 ± 0.51 ml · 100 g-1 · min-1 · mmHg-1) and decreased by NOS inhibition (2.12 ± 0.20 ml · 100 g-1 · min-1 · mmHg-1) and combined inhibition (3.96 ± 0.57 ml · 100 g-1 · min-1 · mmHg-1; all P < 0.05 vs. unblocked). In heart failure rats, renal conductance during unblocked exercise (5.50 ± 0.66 ml · 100 g-1 · min-1 · mmHg-1) was increased by ANG II AT1-receptor blockade (8.48 ± 0.83 ml · 100 g-1 · min-1 · mmHg-1) and decreased by NOS inhibition (2.68 ± 0.22 ml-1 · 100 g-1 · min-1 · mmHg-1; both P < 0.05 vs. unblocked), but it was unaltered during combined inhibition (4.65 ± 0.51 ml · 100 g-1 · min-1 · mmHg- 1). Because our findings during combined blockade could be predicted from the independent actions of NO and ANG II, no interaction was apparent between these two substances in control or heart failure animals. In skeletal muscle, L-NAME-induced reductions in conductance, compared with unblocked exercise (P < 0.05), were abolished during combined inhibition in heart failure but not in control rats. These observations suggest that ANG II causes vasoconstriction in skeletal muscle that is masked by NO-evoked dilation in animals with heart failure. Because reductions in vascular conductance between unblocked exercise and combined inhibition were less than would be predicted from the independent actions of NO and ANG II, an interaction exists between these two substances in heart failure rats. L-NAME-induced increases in arterial pressure during treadmill running were attenuated (P < 0.05) similarly in both groups by combined inhibition. These findings indicate that NO opposes ANG II-induced increases in arterial pressure and in renal and skeletal muscle resistance during dynamic exercise.

AB - We hypothesized that nitric oxide (NO) opposes ANG II-induced increases in arterial pressure and reductions in renal, splanchnic, and skeletal muscle vascular conductance during dynamic exercise in normal and heart failure rats. Regional blood flow and vascular conductance were measured during treadmill running before (unblocked exercise) and after 1) ANG II AT1- receptor blockade (losartan, 20 mg/kg ia), 2) NO synthase (NOS) inhibition [N(G)-nitro-L-arginine methyl ester (L-NAME); 10 mg/kg ia], or 3) ANG II AT1-receptor blockade + NOS inhibition (combined blockade). Renal conductance during unblocked exercise (4.79 ± 0.31 ml · 100 g-1 · min- 1 · mmHg-1) was increased after ANG II AT1-receptor blockade (6.53 ± 0.51 ml · 100 g-1 · min-1 · mmHg-1) and decreased by NOS inhibition (2.12 ± 0.20 ml · 100 g-1 · min-1 · mmHg-1) and combined inhibition (3.96 ± 0.57 ml · 100 g-1 · min-1 · mmHg-1; all P < 0.05 vs. unblocked). In heart failure rats, renal conductance during unblocked exercise (5.50 ± 0.66 ml · 100 g-1 · min-1 · mmHg-1) was increased by ANG II AT1-receptor blockade (8.48 ± 0.83 ml · 100 g-1 · min-1 · mmHg-1) and decreased by NOS inhibition (2.68 ± 0.22 ml-1 · 100 g-1 · min-1 · mmHg-1; both P < 0.05 vs. unblocked), but it was unaltered during combined inhibition (4.65 ± 0.51 ml · 100 g-1 · min-1 · mmHg- 1). Because our findings during combined blockade could be predicted from the independent actions of NO and ANG II, no interaction was apparent between these two substances in control or heart failure animals. In skeletal muscle, L-NAME-induced reductions in conductance, compared with unblocked exercise (P < 0.05), were abolished during combined inhibition in heart failure but not in control rats. These observations suggest that ANG II causes vasoconstriction in skeletal muscle that is masked by NO-evoked dilation in animals with heart failure. Because reductions in vascular conductance between unblocked exercise and combined inhibition were less than would be predicted from the independent actions of NO and ANG II, an interaction exists between these two substances in heart failure rats. L-NAME-induced increases in arterial pressure during treadmill running were attenuated (P < 0.05) similarly in both groups by combined inhibition. These findings indicate that NO opposes ANG II-induced increases in arterial pressure and in renal and skeletal muscle resistance during dynamic exercise.

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