Connexin-mimetic peptides: influence on nitric oxide synthase- and cyclooxygenase-independent renal vasodilatation, basal renal blood flow and blood pressure in the rat

Edhf 2002 ◽  
2001 ◽  
pp. 104-112
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Renal Blood Flow ◽  
Mimetic Peptides ◽  
Oxide Synthase

Nitric oxide synthase and cGMP-mediated stimulation of renin secretion

2001 ◽  
Vol 281 (4) ◽  
pp. R1146-R1151 ◽  
Author(s):  
Cecilia M. Sayago ◽  
William H. Beierwaltes
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Renal Blood Flow ◽  
No Synthase ◽  
Renin Secretion ◽  
Hemodynamic Changes ◽  
Oxide Synthase ◽  
Stimulation Of

The interaction between nitric oxide (NO) and renin is controversial. cAMP is a stimulating messenger for renin, which is degraded by phosphodiesterase (PDE)-3. PDE-3 is inhibited by cGMP, whereas PDE-5 degrades cGMP. We hypothesized that if endogenous cGMP was increased by inhibiting PDE-5, it could inhibit PDE-3, increasing endogenous cAMP, and thereby stimulate renin. We used the selective PDE-5 inhibitor zaprinast at 20 mg/kg body wt ip, which we determined would not change blood pressure (BP) or renal blood flow (RBF). In thiobutabarbital (Inactin)-anesthetized rats, renin secretion rate (RSR) was determined before and 75 min after administration of zaprinast or vehicle. Zaprinast increased cGMP excretion from 12.75 ± 1.57 to 18.67 ± 1.87 pmol/min ( P < 0.003), whereas vehicle had no effect. Zaprinast increased RSR sixfold (from 2.95 ± 1.74 to 17.62 ± 5.46 ng ANG I · h−1 · min−1, P< 0.024), while vehicle had no effect (from 4.08 ± 2.02 to 3.87 ± 1.53 ng ANG I · h−1 · min−1). There were no changes in BP or RBF. We then tested whether the increase in cGMP could be partially due to the activity of the neuronal isoform of NO synthase (nNOS). Pretreatment with the nNOS inhibitor 7-nitroindazole (7-NI; 50 mg/kg body wt) did not change BP or RBF but attenuated the renin-stimulating effect of zaprinast by 40% compared with vehicle. In 7-NI-treated animals, zaprinast-stimulated cGMP excretion was attenuated by 48%, from 9.17 ± 1.85 to 13.60 ± 2.15 pmol/min, compared with an increase from 10.94 ± 1.90 to 26.38 ± 3.61 pmol/min with zaprinast without 7-NI ( P < 0.04). This suggests that changes in endogenous cGMP production at levels not associated with renal hemodynamic changes are involved in a renin-stimulatory pathway. One source of this cGMP may be nNOS generation of NO in the kidney.

scholarly journals Effects of chronic nitric oxide synthase (NOS) inhibition on renal blood flow

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Richard Murray McAllister ◽  
Robert L Johnson ◽  
Sean C Newcomer ◽  
Maurice Harold Laughlin
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Renal Blood Flow ◽  
Oxide Synthase

Selective neuronal nitric oxide synthase inhibition blocks furosemide-stimulated renin secretion in vivo

1995 ◽  
Vol 269 (1) ◽  
pp. F134-F139 ◽  
Author(s):  
W. H. Beierwaltes
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Macula Densa ◽  
Renin Secretion ◽  
Renal Perfusion Pressure ◽  
Neuronal Nos ◽  
Oxide Synthase

The macula densa is a regulatory site for renin. It contains exclusively the neuronal isoform of nitric oxide synthase (NOS), suggesting NO could stimulate renin secretion through the macula densa pathway. To test whether neuronal NOS mediates renin secretion, renin was stimulated by either the renal baroreceptor or the diuretic furosemide (acting through the macula densa pathway). Renin secretion rate (RSR) was measured in 12 Inactin-anesthetized rats at normal (104 +/- 3 mmHg) and reduced renal perfusion pressure (65 +/- 1 mmHg), before and after selective blockade of the neuronal NOS with 7-nitroindazole (7-NI, 50 mg/kg ip). 7-NI had no effect on basal blood pressure (102 +/- 2 mmHg) or renal blood flow (RBF). Decreasing renal perfusion pressure doubled RSR from 11.8 +/- 3.3 to 22.9 +/- 5.7 ng ANG I.h-1.min-1 (P < 0.01) (ANG I is angiotensin I). Similarly, in 7-NI-treated rats, reduced perfusion doubled RSR from 8.5 +/- 1.8 to 20.5 +/- 6.2 ng ANG I.h-1.min-1 (P < 0.01). Renal hemodynamics and RSR were measured in response to 5 mg/kg iv furosemide in 12 control rats and 11 rats treated with 7-NI. Blocking neuronal NOS did not alter blood pressure (102 +/- 2 mmHg), RBF (5.8 +/- 0.4 ml.min-1.g kidney wt-1), or renal vascular resistance (18.7 +/- 1.4 mmHg.ml-1.min.g kidney wt).(ABSTRACT TRUNCATED AT 250 WORDS)

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