Biomedical subjects

M C Khosla

Publications and source records attributed to M C Khosla.

At least 19 recordsLinked to original sources

PubMed1997

Cardiovascular effects produced by microinjection of angiotensins and angiotensin antagonists into the ventrolateral medulla of freely moving rats.

In this study we determined the cardiovascular effects produced by microinjection of angiotensin peptides [Angiotensin-(1-7) and Angiotensin II] and angiotensin antagonists (losartan, L-158,809, CGP 42112A. Sar1-Thr8-Ang II, A-779) into the rostral ventrolateral medulla of freely moving rats. Microinjection of angiotensins (12.5-50 pmol) produced pressor responses associated to variable changes in heart rate, usually tachycardia. Unexpectedly, microinjection of both AT1 and AT2 ligands produced pressor effects at doses that did not change blood pressure in anesthetized rats. Conversely, microinjection of Sar1-Thr8-Ang II and the selective Ang-(1-7) antagonist, A-779, produced a small but significant decrease in MAP an HR. These findings suggest that angiotensins can influence the tonic activity of vasomotor neurons at the RVLM. As previously observed in anesthetized rats, our results further suggest a role for endogenous Ang-(1-7) at the RVLM. The pressor activity of the ligands for AT1 and AT2 angiotensin receptor subtypes at the RVLM, remains to be clarified.

Angiotensin I↗

PubMed1996

Pressor action of angiotensin I at the ventrolateral medulla: effect of selective angiotensin blockade.

In this study we explored the possibility that angiotensin-(1-7) (Ang-(1-7)) is involved in the control of blood pressure at the rostral ventrolateral medulla (RVLM) by determining the effect of angiotensin antagonists (DuP 753 and A-779) and the effect of the angiotensin converting enzyme inhibitor, ramiprilat on the pressor action produced by angiotensin I (Ang I). The pressor effect produced by bilateral microinjection of Ang I into the RVLM of anesthetized rats was not significantly altered by DuP 753 or by the ACE inhibitor ramiprilat. Conversely, the Ang-(1-7) antagonist, A-779, reduced significantly the pressor effect produced by Ang I. These data suggest that in our experimental condition Ang I was preferentially converted to Ang-(1-7) at RVLM, or that Ang I and/or one of its fragments acts through a receptor blocked by A-779.

Angiotensin I↗

PubMed1996

Evidence for a physiological role of angiotensin-(1-7) in the control of hydroelectrolyte balance.

In this study we evaluated the possibility that angiotensin-(1-7) [Ang-(1-7)] acts as an endogenous osmoregulatory peptide by determining the effect of acute administration of its selective antagonist [D-Ala7]Ang-(1-7) (A-779) on renal function parameters in rats. In addition, we investigated the physiological mechanisms involved in the antidiuretic effect of Ang-(1-7). The antidiuretic effect of Ang-(1-7) (40 pmol/0.05 mL per 100 g BW) in water-loaded rats was completely blocked by A-779 (vehicle-treated, 3.34 +/- 0.43 mL/h; Ang-(1-7), 1.48 +/- 0.23; A-779, 2.72 +/- 0.35; Ang-(1-7) plus A-779, 3.26 +/- 0.49). In contrast, the antidiuretic effect of Ang-(1-7) was not significantly changed by a vasopressin V2 receptor antagonist in a dose that completely blocked the antidiuresis produced by an equipotent dose of vasopressin. In addition, Ang-(1-7) administration did not significantly change vasopressin plasma levels in water-loaded rats. The antidiuretic effect of Ang-(1-7) in water-loaded rats was associated with a reduction of creatinine clearance (0.68 +/- 0.04 versus 1.38 +/- 0.32 mL/min in vehicle-treated rats, P <.05) and an increase in urine osmolality (266.8 +/- 32.7 versus 182.8 +/- 14 mOsm/kg in vehicle-treated rats, P <.05). An effect of Ang-(1-7) in tubular water transport was demonstrated in vitro by a fourfold increase in the hydraulic conductivity of inner medullary collecting ducts in the presence of 1 nmol/L Ang-(1-7). Subcutaneous administration of A-779 (2.3 to 9.2 nmol/100 g) produced a significant increase in urine volume (4.6 nmol/100 g, 0.45 +/- 0.12 mL/h; vehicle-treated rats, 0.16 +/- 0.03 mL/h; P <.05) comparable to that of acute administration of a vasopressin V2 receptor antagonist. The diuretic effect of A-779 was associated with an increase in creatinine clearance and decrease in urine osmolality. In contrast, no significant effects on urine volume were observed after systemic administration of angiotensin subtype 1 or 2 receptor antagonists (DuP 753 and CGP 42112A, respectively). These findings suggest that endogenous Ang-(1-7), acting on specific receptors, participates in the control of hydroelectrolyte balance by influencing especially water excretion.

Angiotensin I↗

PubMed1995

Metabolism of angiotensin I in isolated rat hearts. Effect of angiotensin converting enzyme inhibitors.

In this study, the formation of biologically active angiotensins from angiotensin I (Ang I) in isolated rat hearts was evaluated. The role of angiotensin converting enzyme (ACE) in Ang I metabolism was also investigated. HPLC analysis of heart perfusate showed that 125I-Ang I was metabolized extensively (single passage) in the rat coronary circulation in vitro leading to the formation of the biologically active angiotensins: angiotensin II (Ang II), Ang-(2-8), Ang-(3-8) and Ang-(1-7). Ang II was the major product identified in HPLC fractions, corresponding to 7.8 +/- 0.89% of the total radioactivity recovered. A similar profile was observed when single-passage metabolism of non-isotopic Ang I was evaluated by HPLC, followed by radioimmunoassay of the eluate fractions. When 125I-Ang I was perfused in the presence of ACE inhibitors (enalaprilat, ramiprilat) in concentrations up to 130 microM, the formation of Ang II was only partially inhibited (approximately 50%). A similar tendency was observed for Ang-(2-8), Ang-(3-8) and Ang-(2-7). The formation of Ang-(1-7) and its related fragments Ang-(3-7) and Ang-(4-7) was not changed significantly by ACE inhibitors, although a slight increase in formation of these fragments was observed. No significant changes were observed for the carboxyl-terminal fragments of Ang I: Ang-(2-10), Ang-(3-10), and Ang-(4-10). The fractional metabolism of Ang I was not modified by ACE inhibition. These findings suggest that biologically active angiotensins can be formed from Ang I in the rat coronary circulation. These locally generated peptides may contribute to the actions of the renin-angiotensin system in the heart.

Angiotensin I↗

PubMed1995

Angiotensin-(1-7) potentiates the hypotensive effect of bradykinin in conscious rats.

Treatment with angiotensin-converting enzyme inhibitors increases the angiotensin-(1-7) [Ang-(1-7)] and bradykinin concentrations in plasma and tissue. In this study we evaluated the interaction between these peptides by determining the effect of Ang-(1-7) on the hypotensive action of bradykinin in conscious rats. Administration of Ang-(1-7) (5 nmol) did not change mean arterial pressure or heart rate. However, the hypotensive effect of bradykinin, produced by an intravenous or intra-arterial route, was potentiated by Ang-(1-7) in a dose-dependent manner. The Ang-(1-7) doses necessary to transform the effect of a single dose of bradykinin into that produced by a double dose (potentiating unit) were 2 nmol i.v. and 5 nmol IA. The Ang-(1-7) dose used did not change either the pressor effect of Ang II or the hypotensive effect of sodium nitroprusside. The bradykinin-potentiating Ang-(1-7) activity was significantly attenuated by pretreatment with indomethacin (5 mg/kg IM, n = 4). In an additional group the bradykinin-potentiating activity of Ang-(1-7) was evaluated 30 minutes after treatment with the angiotensin-converting enzyme inhibitor enalaprilat (10 mg/kg i.v., n = 9). Under this condition the bradykinin-potentiating activity of Ang-(1-7) was substantially increased, resulting in a potentiating unit of approximately 0.2 nmol IV. Pretreatment with indomethacin (5 mg/kg IM, n = 7) also attenuated the bradykinin-potentiating activity of Ang-(1-7) in enalaprilat-treated rats. These results show that Ang-(1-7) is a bradykinin-potentiating peptide in vivo. Furthermore, the data obtained with indomethacin suggest that prostaglandins participate in the mechanism of the bradykinin potentiation by Ang-(1-7). More importantly, these data suggest that the interaction between Ang-(1-7) and bradykinin can contribute to the pharmacological effects of angiotensin-converting enzyme inhibitors.

Angiotensin I↗

PubMed1994

Losartan, nonpeptide angiotensin II-type 1 (AT1) receptor antagonist, attenuates pressor and sympathoexcitatory responses evoked by angiotensin II and L-glutamate in rostral ventrolateral medulla.

We investigated the effect of losartan, a nonpeptide angiotensin II (Ang II)-type 1 (AT1) receptor antagonist, on the responses evoked by Ang II and L-glutamate (L-Glu) in the rostral ventrolateral medulla (RVLM). Adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were anesthetized with halothane and artificially ventilated. Responses of mean arterial pressure (MAP), heart rate (HR) and splanchnic sympathetic nerve activity (SNA) to microinjection of Ang II (100 pmol) or L-Glu (2 nmol) into the RVLM were examined following microinjection of losartan (10 pmol-10 nmol). Ang II increased MAP (16 +/- 1 mmHg in SHR and 16 +/- 1 mmHg in WKY) and SNA (9 +/- 1% and 10 +/- 1%, respectively), which were significantly (P < 0.01) attenuated by pretreatment with losartan (100 pmol-10 nmol) in both strains. In addition, the pressor and sympathoexcitatory responses evoked by L-Glu were attenuated by losartan in a dose-dependent manner. The increases of MAP evoked by L-Glu (53 +/- 6 mmHg in SHR and 39 +/- 3 mmHg in WKY) were suppressed to 5 +/- 3 mmHg (P < 0.01) and 4 +/- 2 mmHg (P < 0.01), respectively, in the presence of 10 nmol of losartan. The increase of SNA was also markedly inhibited by higher doses of losartan.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1994

Evidence that angiotensin-(1-7) plays a role in the central control of blood pressure at the ventro-lateral medulla acting through specific receptors.

In this study we determined which angiotensin receptors may mediate the cardiovascular effects elicited by angiotensin-(1-7) [Ang-(1-7)] in the rostral ventrolateral medulla (RVLM) and caudal pressor area (CPA) of the ventrolateral medulla (VLM) of anesthetized rats. Furthermore the role of endogenous angiotensins in these areas was also investigated. The pressor effect produced by unilateral microinjection of Ang-(1-7) into the RVLM or CPA was not modified by either the AT1 receptor antagonist, DuP 753 or by the AT2 receptor antagonist, CGP 42112A, but was completely blocked by the Ang-(1-7) selective antagonist, A-779. In contrast, the pressor effect produced by microinjection of angiotensin II (Ang II) was completely blocked by DuP 753 but was not changed by CGP 42112A or A-779. Bilateral microinjection of A-779 into the RVLM or CPA produced a significant fall in mean arterial pressure and heart rate. Microinjection of DuP 753 produced a pressor effect comparable to bilateral injection of vehicle. These results indicate that, although Ang II acts in the VLM through an AT1 receptor subtype, the cardiovascular effects produced by microinjection of Ang-(1-7) into the RVLM and CPA are mediated by a specific angiotensin receptor (AT5?). Furthermore, our data provide evidence that endogenous Ang-(1-7) participates at the VLM in the neural control of arterial blood pressure.

Analysis of Variance↗

PubMed1994

Plasma angiotensin(1-7) immunoreactivity is increased by salt load, water deprivation, and hemorrhage.

In this study we investigated the effects of dehydration and hemorrhage on circulating levels of the heptapeptide, angiotensin(1-7). In water-deprived rats, a twofold increase in plasma angiotensin(1-7) was associated with similar increases in plasma renin activity, and angiotensin I and angiotensin II levels. In salt-loaded rats, plasma angiotensin(1-7) levels increased fourfold; however, other components of the renin-angiotensin system were suppressed or unchanged. In salt-loaded rats, increases in plasma angiotensin II levels in response to hemorrhage in normal rats were severely blunted, whereas angiotensin(1-7) plasma levels increased proportionately to the loss of blood volume. These results suggest that angiotensin(1-7) plasma concentration can be selectively regulated during dehydration and hemorrhage.

Angiotensin I↗

PubMed1994

[7-D-ALA]-angiotensin-(1-7): selective antagonism of angiotensin-(1-7) in the rat paraventricular nucleus.

Microiontophoretic application of both, the octapeptide angiotensin II (Ang II) and its N-terminal heptapeptide angiotensin-(1-7), [Ang-(1-7)], has been shown to increase the firing rate of rat hypothalamic paraventricular neurones. In the present microiontophoretic study, the effect of the angiotensin analogue [7-D-Ala]-Ang-(1-7) on Ang II- and Ang-(1-7)-induced firing rate increase of paraventricular neurones has been tested. While the response to Ang II was unchanged, the response to Ang-(1-7) was effectively blocked by [7-D-Ala]-Ang-(1-7). The results indicate that the Ang-(1-7)-induced excitation of paraventricular neurones may be mediated by a distinct Ang-(1-7)-receptor and that [7-D-Ala]-Ang-(1-7) is a selective antagonist of this receptor.

Action Potentials↗

PubMed1993

Cardiovascular effects produced by micro-injection of angiotensin-(1-7) on vasopressor and vasodepressor sites of the ventrolateral medulla.

In this study, we determined the cardiovascular effects produced by micro-injection of the heptapeptide Angiotensin-(1-7) [Ang-(1-7)] into the rat ventrolateral medulla (VLM). Micro-injection of Ang-(1-7) into the rostral VLM and the caudal pressor area of the VLM produced significant increases in arterial pressure, comparable to that observed with micro-injection of Ang II. The changes in arterial pressure were associated with more variable changes in heart rate (HR) (usually tachycardia). On the other hand, micro-injection of Ang-(1-7) into the caudal depressor area induced decreases in arterial pressure and HR. The results suggest that, besides Ang II, Ang-(1-7) is involved in the mediation of the cardiovascular actions of the renin-angiotensin system in the VLM.

Angiotensin I↗

PubMed1993

Differential responses to angiotensin-(1-7) in the feline mesenteric and hindquarters vascular beds.

Regional vascular responses to angiotensin (Ang)-(1-7), a heptapeptide derivative of Ang II were investigated in the feline hindquarters and mesenteric vascular beds under conditions of controlled flow. In the mesenteric vascular bed, injections of Ang-(1-7) in doses of 1, 3 and 10 micrograms produced dose-dependent decreases in mesenteric perfusion pressure whereas at doses of 30 and 100 micrograms, increases were observed. In contrast, in the hindquarters circulation, low doses produced increases while high doses produced decreases in perfusion pressure. In both vascular beds the degree of vasoconstriction was weak, being less than 1% of that elicited by Ang II. The vasoconstrictor effect of Ang-(1-7) in both the mesenteric and hindquarters vascular bed was blocked by DuP 753 (1 mg/kg i.v.), an Ang receptor subtype 1 (AT1) antagonist. The vasodilator responses in both vascular beds were partially blocked by the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (100 mg/kg i.v.) but were unaffected by the cyclooxygenase inhibitor, meclofenamate (2.5 mg/kg i.v.). The present results show that in the peripheral vascular bed of the cat, Ang-(1-7) causes vasodilation or modest vasoconstriction, depending on the dose and the regional vascular bed studied. The present data also suggest that the vasodilator effect of the peptide may be mediated in part by the release of endothelium-derived relaxing factor and the vasoconstrictor effect by activation of the AT1 receptor subtype.

Amino Acid Oxidoreductases↗

PubMed1993

Effects of angiotensin I of the American bullfrog Rana catesbeiana on amphibian tissues.

1. The effect of bullfrog angiotensin I [Asp1, Val5, Asn9] angiotensin I, (AT I) on short-circuit current (SCC) on isolated toad skin and aorta contractility was examined. 2. AT I increased SCC in toad skin, the effect was partially inhibited by angiotensin-converting enzyme inhibitor (ACEI) teprotide. 3. AT I induced contractile responses in isolated rings of toad aorta. This effect was partially inhibited by captopril and completely blocked by the peptide antagonist [Sar1, Ile8] angiotensin II. 4. Present results indicate that this homologue AT I would act in amphibian tissues by conversion to AT II.

Angiotensin I↗

PubMed1993

Modulation of phospholipase A2 activity and sodium transport by angiotensin-(1-7).

Angiotensin II (Ang II) receptors are coupled to a variety of signal transduction mechanisms. In the kidney, Ang II at nanomolar concentration binds to proximal tubular cells and stimulates phospholipase A2 (PLA2), which in turn catalyzes the hydrolysis of phosphatidylcholine into lysophosphatidylcholine (LPC) and fatty acid. This signal transduction pathway has been shown to be an important modulator of sodium transport. The kidney cortex possesses the enzyme necessary to convert angiotensin I (Ang I) directly to Ang-(1-7) bypassing Ang II as an intermediate. The present investigation was undertaken to determine whether Ang-(1-7) influences epithelial cell function by comparing this heptapeptide with Ang II as a modulator of PLA2 activity and sodium transport. Proximal tubular cells were labeled in tissue culture with 3H-choline and PLA2 activity was measured by quantitation of LPC. We found that Ang II (10(-9) M to 10(-6) M) significantly increased PLA2 activity (154 +/- 36% to 209 +/- 94%). Similar results were obtained with Ang-(1-7) (240 +/- 130% to 353 +/- 40%). The bioactivity of the peptides was assayed by its ability to regulate transcellular 22Na flux. Ang II (10(-9) M) inhibited 22Na flux by 12 +/- 2% while Ang-(1-7) (10(-9) M) inhibited 22Na flux by 20 +/- 5%. These results suggest that one potential role of Ang-(1-7) in the regulation of kidney epithelial electrolyte transport may involve activation of PLA2.

8,11,14-Eicosatrienoic Acid↗

PubMed1993

Angiotensin II-induced endothelium-dependent relaxation of fowl aorta.

In the domestic fowl, angiotensin II (ANG II) decreases blood pressure in vivo and causes endothelium-dependent relaxation of aortic smooth muscles in vitro. To characterize ANG II-induced vasorelaxation, we compared endothelium-dependent vasodilatory effects of [Asp1,Val5]-ANG II (fowl ANG II) and acetylcholine (ACh) with the endothelium-independent vasorelaxing effect of sodium nitroprusside (SNP) on isometric tension of fowl aortic rings. Hemoglobin (Hb), gossypol, and N omega-nitro-L-arginine methyl ester (L-NAME), inhibitors for endothelium-derived relaxing factor (EDRF) in mammalian blood vessels, partially inhibited vasorelaxation induced by ANG II and ACh in fowl. Hb also markedly attenuated SNP-induced vasorelaxation, but not 8-bromoguanosine 3',5'-cyclic monophosphate-induced relaxation. 3,4,5-Trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8) or the removal of Ca2+ from the bathing medium attenuated the ACh-induced relaxation but did not significantly reduce vasorelaxation induced by ANG II or SNP. In the zero Ca2+ medium, aortic rings showed tachyphylaxis to ACh, while ANG II caused tachyphylaxis regardless of the presence or absence of external Ca2+. Furthermore, pretreatment of the ring with a high dose of ACh abolished the vasorelaxation response to ANG II, suggesting that ACh and ANG II may share a common Ca2+ pool. Calmidazolium, a calmodulin antagonist, abolished the vasorelaxation induced by ANG II and ACh but not that by SNP. Comparison of the vasodilatory effects of several ANG II analogues on fowl aortic rings showed an approximate potency order of [Asp1,Val5]-ANG II = [Asp1,Ile5]-ANG II > [Asn1,Ile5]-ANG II = [Sar1,Ile5]-ANG II > [Val5]-ANG III.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1993

Role of nitric oxide and angiotensin II in the regulation of sympathetic nerve activity in spontaneously hypertensive rats.

This study evaluated the actions of nitric oxide on the blood pressure and renal sympathetic nerve activity responses produced by angiotensin II (Ang II) blockade in conscious spontaneously hypertensive rats. Two days after implantation of electrodes, we measured mean arterial pressure, heart rate, and renal sympathetic nerve activity. Baroreceptor reflex function was assessed with a logistic function curve; the maximum slope of the curve estimated the baroreceptor reflex gain. Data were obtained in rats given acute intravenous administration of either vehicle, the Ang II type 1 receptor antagonist losartan, the type 2 antagonist CGP 42112A, or the converting enzyme inhibitor lisinopril. In comparison with vehicle (-1.1 +/- 0.2%/mm Hg), both losartan (-1.8 +/- 0.3%/mm Hg) and lisinopril (-2.4 +/- 0.2%/mm Hg) significantly increased the maximum gain of the baroreceptor reflex control of nerve activity (p < 0.05). In contrast, the type 2 receptor antagonist did not alter baroreceptor reflex function. Similar studies were performed in rats that received an intravenous injection of NG-monomethyl L-arginine (10 mg/kg). The nitric oxide synthase inhibitor increased baseline blood pressure and decreased renal sympathetic nerve activity. Subsequent administration of losartan or lisinopril returned blood pressure to initial hypertensive level, whereas sympathetic nerve activity was increased to a level above the initial control value. The maximum gain of the baroreceptor reflex control of renal nerve activity was increased after the nitric oxide inhibition. The present study demonstrates that blunted baroreceptor reflex function in conscious spontaneously hypertensive rats is mediated by an Ang II type 1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1992

Effects of angiotensin II and its selective antagonists on inferior olivary neurones.

On the basis of biochemical and autoradiographic studies it has been shown that the inferior olivary nucleus (ION) contains predominantly angiotensin II (Ang II) receptors of the subtype 2 (AT2). In the present investigation we used microiontophoretic techniques to test the effect of Ang II on the spontaneous firing rate of rat neurones in the ION in vivo. Ang II excited the majority of histologically identified ION neurones. Furthermore, the antagonism of this angiotensin-induced excitation by selective angiotensin receptor blockers of subtype 1 and 2 (AT1 and AT2) was examined. The excitation could be blocked by low doses of the AT2-antagonists PD 123177 and CGP 42112A, whereas the AT1-antagonist DuP 753 was ineffective even at high doses. On a few occasions, however, ejection of the AT1-antagonist resulted in a potentiation of angiotensin-induced excitation. The results suggest that Ang II has an excitatory effect on a considerable number of ION neurones and that this effect is mediated by AT2-receptors.

Angiotensin II↗

PubMed1992

Effects of angiotensin analogues and angiotensin receptor antagonists on paraventricular neurones.

In a previous study we observed that most neurones in the paraventricular nucleus are excited by angiotensin-(1-7). In comparison with angiotensin III this excitatory action was significantly delayed. The aim of the present microiontophoretic study of angiotensin II-sensitive rat paraventricular neurones was to compare the effect of the angiotensin-analogues angiotensin-(1-7), angiotensin-(2-7), angiotensin II and angiotensin III on the spontaneous activity of these neurones and to test angiotensin receptor subtype 1 antagonists (CGP 46027 or DuP 753) and subtype 2 selective antagonists (CGP 42112A and PD 123177) in order to acquire more evidence of the receptor subtype present. As previously observed angiotensin II, angiotensin III and angiotensin-(1-7) excited most neurones. The effect of angiotensin-(1-7) was usually weaker than that of angiotensin II, and in contrast to angiotensin III the latencies were not significantly different. Angiotensin-(1-7) seemed to be active by itself, because its effect was antagonised by angiotensin receptor antagonists. Angiotensin-(2-7) was mostly inactive, although a few cells were excited. Whereas the excitatory effects of angiotensin-(1-7), angiotensin II and angiotensin III could always be inhibited with both angiotensin receptor subtype antagonists 1 and 2, that produced by angiotensin-(2-7) was only weakly antagonised, if at all. Subtype 1 selective antagonists were effective at lower concentrations than selective subtype 2 antagonists.

Angiotensin II↗

PubMed1992

Differential baroreceptor reflex modulation by centrally infused angiotensin peptides.

The present study was designed to investigate the effect of intracerebroventricular (icv) and intravenous (iv) infusion of angiotensin (ANG)-(1-7), ANG III, and ANG II on the baroreceptor control of heart rate (BHR) in conscious rats. Reflex changes in HR were elicited by bolus iv injection of either phenylephrine or sodium nitroprusside before and within 1 and 3 h of icv infusion of ANG II (n = 10), ANG III (n = 9), ANG-(1-7) (n = 9), or saline (n = 9) at a rate of 3 nmol.7.5 microliter-1.h-1. In another group of animals (n = 23), iv infusion of the same amount of ANG peptides was carried out at a rate of 0.7 ml/h. The average ratio of changes in HR in beats per minute and changes in mean arterial pressure (MAP, mmHg) was used as an index of BHR sensitivity. ANG II and ANG III produced a significant increase in the basal levels of MAP, but only during the first hour of infusion (iv or icv). No significant changes in baseline HR were observed. ANG-(1-7) and saline infusion did not change basal levels of HR or MAP (iv or icv). ANG II (iv and icv) and ANG III (icv) caused a significant decrease in the BHR sensitivity for reflex bradycardia. In contrast, icv infusion of ANG-(1-7) induced a significant increase in BHR sensitivity for reflex bradycardia (-3.0 +/- 0.3, 1 h, and -2.8 +/- 0.1 beats.min-1.mmHg-1, 3 h vs. -2.1 +/- 0.2 beats.min-1.mmHg-1, before infusion).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗