PubMed HealthSearch

PubMed · 2528402

Angiotensin restores atrial natriuretic factor-induced decrease of baroreceptor sensitivity in normotensive rats, but not in spontaneously hypertensive rats.

Abstract

The effect of atrial natriuretic factor (ANF) on baroreflex sensitivity was determined in unanesthetized normotensive (Wistar-Kyoto, WKY) or spontaneously hypertensive rats (SHR) during acute hypertensive stimuli (phenylephrine) or hypotensive stimuli (sodium nitroprusside). The i.v. dose of rat ANF [( Ser99,Tyr126]ANF) was 50 ng/min per rat, sufficient to decrease mean arterial blood pressure (ABP) by about 6 mmHg (1 mmHg = 133.3 Pa) in WKY. SHR showed no change in ABP with this ANF dose. During a control infusion of physiological saline, the mean heart rate (HR) response to increases in ABP was -1.30 +/- 0.27 beats/min (bpm)/mmHg in WKY and -0.37 +/- 0.22 in SHR (p less than 0.05). These values were not affected significantly by ANF. However, ANF blunted chronotropic responses to ABP decreases. The control values of the delta HR/delta ABP slope in WKY and SHR were -2.34 +/- 0.57 and -2.01 +/- 0.37 bpm/mmHg, respectively. In the presence of ANF, the slope changed to -0.36 +/- 0.43 (i.e., bradycardia in response to hypotension) in WKY and to +0.20 +/- 0.21 in SHR (p less than 0.005 for the difference from control for both). This ANF-induced loss of baroreflex sensitivity was reversed in WKY by the addition of angiotensin I (sufficient to increase ABP by 5 mmHg in control rats). Angiotensin did not restore baroreflex sensitivity in ANF-infused SHR, and ANF had no effect on the ABP increase caused by angiotensin in either group. The data suggest that ANF does not act on baroreceptor structures directly, but inhibits mechanisms involved in efferent sympathetic activation. Parasympathetic responses do not appear to be compromised.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

U Ackermann, T G Irizawa, B Barber. 1989. Angiotensin restores atrial natriuretic factor-induced decrease of baroreceptor sensitivity in normotensive rats, but not in spontaneously hypertensive rats.. https://doi.org/10.1139/y89-108

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

The two homologous domains of human angiotensin I-converting enzyme interact differently with competitive inhibitors.

The endothelial angiotensin I-converting enzyme (ACE; EC 3.4.15.1) has recently been shown to contain two large homologous domains (called here the N and C domains), each being a zinc-dependent dipeptidyl carboxypeptidase. To further characterize the two active sites of ACE, we have investigated their interaction with four competitive ACE inhibitors, which are all potent antihypertensive drugs. The binding of [3H] trandolaprilat to the two active sites was examined using the wild-type ACE and four ACE mutants each containing only one intact domain, the other domain being either deleted or inactivated by point mutation of the zinc-coordinating histidines. In contrast with all the previous studies, which suggested the presence of a single high affinity inhibitor binding site in ACE, the present study shows that both the N and C domains of ACE contain a high affinity inhibitor binding site (KD = 3 and 1 X 10(-10) M, respectively, at pH 7.5, 4 degrees C, and 100 mM NaCl). Chloride stabilizes the enzyme-inhibitor complex for each domain primarily by slowing its dissociation rate, as the k-1 values of the N and C domains are markedly decreased (about 30- and 1100-fold, respectively) by 300 mM NaCl. At high chloride concentrations, the chloride effect is much greater for the C domain than for the N domain resulting in a higher affinity of this inhibitor for the C domain. In addition, the inhibitory potency of captopril (C), enalaprilat (E), and lisinopril (L) for each domain was assayed by hydrolysis of Hip-His-Leu. Their Ki values for the two domains are all within the nanomolar range, indicating that they are all highly potent inhibitors for both domains. However, their relative potencies are different for the C domain (L greater than E greater than C) and the N domain (C greater than E greater than L). The different inhibitor binding properties of the two domains observed in the present study provide strong evidence for the presence of structural differences between the two active sites of ACE.

Angiotensin I

Laser desorption studies of high mass biomolecules in Fourier-transform ion cyclotron resonance mass spectrometry.

Matrix-assisted laser desorption ionization is used to obtain Fourier-transform ion cyclotron resonance mass spectra of model peptides (e.g., gramicidin S, angiotensin I, renin substrate, melittin, and bovine insulin). Matrix-assisted laser desorption ionization yields ions having appreciable kinetic energies. Two methods for trapping the high kinetic energy ions are described: (i) the ion signal for [M+H]+ ions is shown to increase with increasing trapping voltages, and (ii) collisional relaxation is used for the detection of [M+H]+ ions of bovine insulin.

Angiotensin I

Comparison of angiotensin-converting enzyme inhibitors in the rat in perfused hindlimbs and in vivo.

To investigate the role of local renin angiotensin systems in the functional responses to angiotensin I and II, the effects of angiotensin I and angiotensin II on resistance were measured in perfused hindlimbs of rats under normal conditions and during infusion of enalaprilate, lisinopril, zabiciprilate and captopril at two infusion rates. The angiotensin-converting enzyme (ACE) inhibitors significantly increased ED50 and decreased maximal resistance changes of angiotensin I dose dependently, without effects on angiotensin II responses. Captopril increased the ED50 of angiotensin I significantly more than did the other ACE inhibitors at a low infusion rate. The ACE inhibitors, except for lisinopril, increased the ED50 of angiotensin I pressor responses in vivo to the same extent, and were similarly potent to inhibit plasma ACE activity at 15 min after injection. The ratio of the doses of the ACE inhibitors used in vivo was the same as in perfused hindlimbs. These results suggest that, in the hindlimbs, angiotensin I causes ACE-dependent vasoconstriction. Captopril may be more effective to inhibit local ACE than the other ACE inhibitors investigated.

Angiotensin I