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Biomedical subjects

C M Ferrario

Publications and source records attributed to C M Ferrario.

At least 109 records · Page 6Linked to original sources
PubMed1993

Ventrolateral medulla in spontaneously hypertensive rats: role of angiotensin II.

We investigated whether angiotensin II (ANG II), endogenous to the ventrolateral medulla (VLM), contributes to cardiovascular regulation in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The action of ANG II endogenous to the VLM was examined by microinjection of 100 pmol of [Sar1,Thr8]ANG II into either the rostral (R) or caudal (C) VLM. This ANG II antagonist caused depressor and bradycardic responses in the RVLM and pressor and tachycardic responses in the CVLM. The magnitude of the blood pressure responses was significantly greater (P < 0.01 in RVLM and P < 0.05 in CVLM) in SHRs (-27 +/- 3 mmHg in RVLM and 29 +/- 4 mmHg in CVLM) than in WKY rats (-17 +/- 1 and 17 +/- 2 mmHg, respectively). Suppression of tonic activity of RVLM neurons by bilateral injection of muscimol in the RVLM showed that the pressor response produced by ANG II antagonist injection in the CVLM required the integrity of rostral pressor neurons. The present data suggest that ANG II endogenous to RVLM and CVLM acts as a tonic excitatory agent on vasomotor neurons of the VLM. The contribution of ANG II in the RVLM and CVLM to the prevailing level of blood pressure was significantly (P < 0.01) larger in SHRs vs. WKY rats when the effect of ANG II blockade was measured as the change in blood pressure. Blockade of gamma-aminobutyric acid (GABA)A receptors in the RVLM showed that inhibitory GABAergic input to the RVLM was not diminished in this strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
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↗
PubMed1993

Alterations in prostaglandin production in spontaneously hypertensive rat smooth muscle cells.

We have characterized angiotensin binding sites in cultured smooth muscle cells obtained from the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. In both strains of rats the binding of 125I-angiotensin II (125I-Ang II) in smooth muscle cells was time dependent and reached a maximum at 60 minutes. Scatchard analysis revealed a single binding site in both strains with equilibrium constants (KD) of 5.35 nmol/L in SHR and 3.47 nmol/L in WKY rats. Binding capacities (Bmax) in smooth muscle cells averaged 270 and 150 fmol/mg protein in SHR and WKY rats, respectively. Angiotensin peptides competed for 125I-Ang II binding with an order of potency of Ang II > angiotensin-(1-7) = angiotensin I. In smooth muscle cells of the SHR, basal prostaglandin E2 (PGE2) and prostacyclin (prostaglandin I2 [PGI2]) release were threefold and 15-fold lower than that found in WKY rat smooth muscle cells. Ang II as well as angiotensin-(1-7) stimulated PGE2 and PGI2 release in WKY rat smooth muscle cells. In smooth muscle cells from SHR, Ang II increased the production of both PGE2 and PGI2, whereas angiotensin-(1-7) enhanced only PGE2 but not PGI2 release. There was no significant difference between Ang II-stimulated PGE2 and PGI2 release or angiotensin-(1-7)-stimulated PGE2 production in SHR and WKY rat smooth muscle cells. However, angiotensin-(1-7)-stimulated PGI2 release was significantly lower (p < 0.0005) in SHR compared with WKY smooth muscle cells. Collectively, the data suggest that smooth muscle cells of SHR contain a higher number of angiotensin binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1993

Effects of large and small transections of the preoptic-hypothalamic region on hydromineral regulation in rats.

To further elucidate the role of the preoptic-hypothalamic region in fluid and electrolyte balance we studied the effect of surgical preoptic-hypothalamic disconnection using either a large (preoptic-hypothalamic disconnection) or a small (medial preoptic-hypothalamic disconnection) microknife. Both the large and small cuts seemed to transect the posterior projection originating in the periventricular tissue surrounding the anteroventral third ventricle (AV3V) and extending to supraoptic nucleus, but the supraoptic-neurohypophysial pathway was severed only by the large cut. Seven-day metabolic studies showed a disruption in hydromineral balance only in large cut rats; they had increased water intake and urine volume on day 1, a near-recovery of function on days 2 and 3, and polydipsia and polyuria on days 4 to 7. There was no difference between small cut rats and sham-operated rats in metabolic measurements. The large cut rats also had sustained hypernatremia and hyperosmolality, which was enhanced after water restriction for 48 h but was not accompanied by an increase in plasma arginine vasopressin. Our data therefore suggest that the efferent fibers running caudally from the AV3V are not involved in mediation of the hydromineral regulation of the AV3V.

Animals↗
PubMed1993

Nocturnal hypotension and ACE inhibitors.

Thirty essential hypertensive subjects had their BP measured by 24h ambulatory monitoring before (first placebo period) and after exposure to antihypertensive therapy with either enalapril (four weeks) or nitrendipine (six weeks). Similar measures of BP were obtained during a second placebo period intercalated between the two active drugs. The 24h averages of systolic and diastolic pressures were higher during placebo (148 +/- 3/91 +/- 1 mmHg, respectively) than during treatment periods. Four weeks of treatment with enalapril reduced arterial pressure to a 24h average of 137 +/- 1/86 +/- 1 mmHg while nitrendipine given for six weeks lowered BP to an average of 135 +/- 1/84 +/- 1 mmHg. The antihypertensive effect of the drugs was of a comparable magnitude (P > 0.05). In addition both drugs produced analogous reductions in BP during the day (07.00 to 23.00 h). In contrast, the nocturnal fall in BP was significantly greater during treatment with nitrendipine. Average systolic and diastolic pressures between 23.00 h and 07.00 h were 133 +/- 1 mmHg and 82 +/- 2 mmHg with enalapril compared with 129 +/- 3 mmHg (P < 0.01) and 77 +/- 3 mmHg (P < 0.01) with nitrendipine, respectively. These data suggest that antihypertensive agents show important differences in terms of their action on the mechanisms that regulate BP during sleep. Medications that amplify the otherwise physiological fall in BP during sleep may add risk to patients with impaired coronary vasodilator reserve owing to ventricular hypertrophy, coronary atherosclerosis, or both.

Adult↗
PubMed1993

Fentanyl attenuates porcine coronary arterial contraction through M3-muscarinic antagonism.

The "antimuscarinic effect" of fentanyl and its dependence on subtypes of receptors were characterized in isolated porcine coronary arteries. Left anterior descending coronary arteries were dissected from the hearts of 60 adult pigs obtained at a slaughterhouse and prepared for isometric tension studies. The effects of fentanyl on the cumulative concentration-response curve for acetylcholine were obtained in the presence and absence of muscarinic blockade by atropine. Fentanyl shifted the concentration-response curve to the right in a concentration-dependent fashion. Atropine shifted the concentration-response curve to the right, and no further shift was caused by fentanyl. To investigate the dependence on muscarinic receptor subtypes, the effect of fentanyl on acetylcholine-induced contraction was examined in the presence of specific M1-, M2-, and M3-muscarinic antagonists. The pA2 values for fentanyl decreased significantly in the presence of atropine (a nonspecific antagonist) and also in the presence of p-F-HHSiD (an M3-antagonist). In contrast, no significant change of pA2 value for fentanyl was observed in the presence of both pirenzepine (an M1-antagonist) and methoctramine (an M2-antagonist). We conclude that fentanyl has an antimuscarinic effect, and that this antagonism occurs in a competitive manner. Furthermore, the significant decrease of the pA2 value for fentanyl in the presence of M3-, but not in the presence of M1 + M2-antagonists, suggests that the attenuation of cholinergic contraction of porcine coronary arteries by fentanyl is mediated through the M3-muscarinic receptor subtype.

Acetylcholine↗
PubMed1993

Differential regulation of prostaglandin synthesis by angiotensin peptides in porcine aortic smooth muscle cells: subtypes of angiotensin receptors involved.

We determined the role of AT1 and AT2 angiotensin receptors as mediators of prostaglandin (PG) release and mobilization of intracellular Ca++ in cultures of porcine vascular smooth muscle cells (VSMC) with subtype-selective angiotensin (Ang) II receptor antagonists. The binding of [125I]Ang II to porcine VSMC showed an equilibrium constant (KD) of 0.52 nM and a binding capacity (Bmax) of 14.8 fmol/mg protein. Using the AT1 antagonists DuP 753, its metabolite EXP 3174, and L-158,809, [125I]Ang II binding was displaced in a clearly biphasic manner, indicating the presence of two binding sites. Consistent with this, the AT2 antagonist CGP 42112A also displayed a biphasic curve, whereas another AT2 antagonist, PD 123177, showed a 20% reduction in binding. Ang I, Ang II and Ang-(1-7) stimulated PGE2 as well as PGI2 synthesis in a dose-dependent pattern. Ang II but not Ang I or Ang-(1-7) also caused an increase in the intracellular concentration of Ca++. Ca++ mobilization by Ang II was blocked by the AT1 antagonist DuP 753, but not by the AT2 antagonists. Ang II- and Ang I-stimulated (10 nM) PG production was attenuated by all three AT1 antagonists. However, both CGP 42112A (100 nM) and PD 123177 (100 nM) also attenuated PG release in response to Ang II. The enhancement in PG release by Ang I (10 nM) was significantly reduced by CGP 42112A (100 nM), but not by PD 123177 (1 microM). Of the AT1 antagonists, only high doses of DuP 753 or L-158,809 partially reduced the Ang-(1-7)-induced release of PG. CGP 42112A was ineffective for blocking Ang-(1-7)-stimulated PG release. Ang-(1-7)-stimulated PGE2 and PGI2 production was significantly reduced by PD 123177. Unlike DuP 753 or L-158,809, but similar to the sarcosine antagonists, EXP 3174 (10 nM) abolished the angiotensin peptide-induced PG production. These data show that Ang I and Ang II stimulate PGE2 and PGI2 release via activation of both AT1 and AT2 receptors in porcine VSMC. Ang II stimulates intracellular Ca++ mobilization via activation of AT1 receptors only. Because Ang-(1-7) enhanced PGE2 and PGI2 release via activation of angiotensin receptors having greater affinity for PD 123177 than CGP 42112A, although CGP 42112A showed a greater ability to block the Ang I response, these data further suggest differences in these two compounds at AT2 receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin Receptor Antagonists↗
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

Peripheral and central angiotensin II regulates expression of genes of the renin-angiotensin system.

We investigated whether angiotensin (ANG) II has the potential to regulate expression of genes of the renin-angiotensin system (RAS) in peripheral and central tissues. ANG II (0.1 or 6.0 nmol/h) was infused by osmotic minipump into male Sprague-Dawley rats (225-250 g) for 5 days, either intravenously or intracerebroventricularly. We measured angiotensinogen mRNA in liver, adrenal glands, and brain (hypothalamus and lower brain stem), renin mRNA in the kidney, and angiotensin-converting enzyme (ACE) mRNA in the lung and testis by Northern blot analysis. We demonstrated that plasma ANG II increases the levels of liver angiotensinogen mRNA, decreases kidney renin mRNA, and decreases lung ACE mRNA. Intracerebroventricular administration of ANG II resulted in a different pattern of responses of the peripheral RAS components. Liver angiotensinogen mRNA was increased, and kidney renin mRNA was decreased by both doses of ANG II, whereas lung ACE mRNA remained unresponsive at either dose. Centrally mediated influences of ANG II are most likely indirect since plasma ANG II concentration was not changed. This study has revealed that ANG II has profound diverse effects that influence the regulation of its formation. Further, results indicate that genes of the RAS responded to exogenous ANG II in both tissue- and route-specific ways.

Angiotensin II↗
PubMed1992

Renal nerve activity in rats with spontaneous hypertension: effect of converting enzyme inhibitor.

We studied the effects of chronic oral inhibition of angiotensin-converting enzyme on the baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) in 14-wk-old conscious spontaneously hypertensive rats (SHR; n = 12) and age-matched Wistar-Kyoto rats (WKY; n = 11). Rats were treated with lisinopril (10 mg.kg-1.day-1 in tap water) or vehicle for 7 days. We evaluated the baroreflex control of efferent RSNA and HR in awake rats 2 days after implantation of electrodes around the renal sympathetic nerves. The relation between mean arterial pressure (MAP) and either RSNA or HR was analyzed by a logistic function curve during intravenous infusions of phenylephrine and nitroglycerin. The maximum gain of the curve was considered as the sensitivity of the baroreflex. MAP in lisinopril-treated SHR averaged 93 +/- 3 mmHg, a value lower than that obtained in vehicle-treated SHR (147 +/- 5 mmHg) but not in WKY (96 +/- 4 mmHg). In vehicle-treated SHR baroreflex sensitivity (-4.3 +/- 0.5% change nerve activity/mmHg) was significantly (P less than 0.005) smaller than that of WKY (-15.8 +/- 1.5%/mmHg). Seven days of oral treatment of lisinopril caused significant improvement of the baroreflex sensitivity in SHR (-10.5 +/- 0.7%/mmHg, P less than 0.01). The maximum gain of MAP and HR relation of lisinopril-treated SHR was also larger (P less than 0.05) than that of vehicle-treated SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Stimulation of endothelial cell prostaglandin production by angiotensin peptides. Characterization of receptors.

Angiotensin II stimulates prostaglandin release in blood vessels via activation of angiotensin receptors present in endothelium, vascular smooth muscle cells, or both. We evaluated the response of angiotensin II, angiotensin I, and [des-Phe8] angiotensin II [angiotensin-(1-7)] on prostaglandin release in porcine aortic endothelial cells. Incubation of cell monolayers with angiotensin I and angiotensin-(1-7), but not angiotensin II, stimulated the release of prostaglandin E2 and prostaglandin I2 in a dose-dependent manner (10(-10) to 10(-6) M) with an EC50 of approximately 1 nM. In addition, we characterized the angiotensin receptor subtypes mediating prostaglandin synthesis by using subtype-selective antagonists. Angiotensin I-stimulated prostaglandin synthesis was not altered by either of the nonselective classical angiotensin receptor antagonists [Sar1,Thr8]angiotensin II or [Sar1,Ile8]angiotensin II. In contrast, either the angiotensin subtype 1 (AT1) antagonist DuP 753 or the subtype 2 (AT2) antagonist CGP42112A significantly attenuated the prostaglandin release in response to angiotensin I. However, PD123177, another AT2 antagonist, did not inhibit angiotensin I-stimulated prostaglandin release. Angiotensin-(1-7)-induced prostaglandin release was significantly attenuated by [Sar1,Thr8]angiotensin II (10(-6) M) and PD123177 (10(-6) M) but not by [Sar1,Ile8]angiotensin II, DuP 753, or CGP42112A. Higher doses (10(-5) M) of DuP 753 and CGP42112A attenuated the angiotensin-(1-7) response. These data suggest that in porcine aortic endothelial cells, angiotensin I and angiotensin-(1-7) but not angiotensin II are potent stimuli for prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1992

Production of angiotensin-(1-7) by human vascular endothelium.

The heptapeptide angiotensin-(1-7) is a circulating biologically active product of the renin-angiotensin system. In this study, we evaluated the role of the vascular endothelium in the formation of angiotensin-(1-7). Metabolism of 125I-angiotensin I was investigated using confluent cultured bovine and human aortic and umbilical vein endothelial cells. The fetal calf serum-supplemented medium was replaced by serum-free medium containing 0.2% bovine serum albumin. One hour later, this medium was replaced by serum-free medium containing 125I-angiotensin I. After incubation of 125I-angiotensin I for various intervals at 37 degrees C, the medium was collected and analyzed for formed products by high-performance liquid chromatography. Products of angiotensin I metabolism were identified by comparison of their retention times with those of radiolabeled standards. The contribution of proteases released into the medium was evaluated by incubation of 125I-angiotensin I with medium previously incubated for 1 hour with endothelial cells. Incubation of 125I-angiotensin I with bovine and human endothelial cells produced a time-dependent generation of 125I-angiotensin-(1-7) greater than 125I-angiotensin II greater than 125I-angiotensin-(1-4). Generation of angiotensin peptides was not due to the presence of proteases in the medium. When human umbilical endothelial cells were incubated in the presence of the angiotensin converting enzyme inhibitor enalaprilat (1 microM), generation of angiotensin II was undetectable. In contrast, angiotensin-(1-7) production increased by an average of 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1992

In vivo metabolism of angiotensin I by neutral endopeptidase (EC 3.4.24.11) in spontaneously hypertensive rats.

We investigated the processing enzymes involved in the formation of circulating angiotensin-(1-7) after intravenous administration of angiotensin I to conscious spontaneously hypertensive and Wistar-Kyoto rats. Immunoreactive products, including angiotensin I, angiotensin II, and angiotensin-(1-7), were measured in arterial blood by three specific radioimmunoassays. Angiotensin I infusion (2 nmol) induced a rapid increase in immunoreactive angiotensin II and angiotensin-(1-7). Pretreatment with the angiotensin converting enzyme inhibitor enalaprilat (2 mg/kg) eliminated angiotensin II formation and augmented circulating levels of angiotensin I and angiotensin-(1-7) in spontaneously hypertensive and Wistar-Kyoto rats. The elevated levels of angiotensin-(1-7) in enalaprilat-treated rats were blocked by concurrent treatment with the neutral endopeptidase (EC 3.4.24.11) inhibitor SCH 39,370 (15 mg/kg) in both strains. Administration of SCH 39,370 alone decreased angiotensin-(1-7) levels in spontaneously hypertensive rats, whereas angiotensin II levels increased in both strains (p less than 0.01). Comparisons of the metabolism of angiotensin I in the two rat strains showed increased formation of angiotensin-(1-7) in spontaneously hypertensive rats not given any of the enzyme inhibitors. In addition, levels of angiotensin I were higher after administration of SCH 39,370 in hypertensive rats. These novel findings reveal that neutral endopeptidase EC 3.4.24.11 participates in the conversion of angiotensin I to angiotensin-(1-7) and in the metabolism of angiotensin II in the circulation of both spontaneously hypertensive and Wistar-Kyoto rats. Our results suggest that neutral endopeptidase EC 3.4.24.11 is a major enzymatic constituent of the circulating renin-angiotensin system.

Angiotensin I↗
PubMed1992

Tissue renin-angiotensin systems in renal hypertension.

Angiotensinogen messenger RNA (mRNA) levels were measured in the brain (hypothalamus, lower brain stem, cerebellum), liver, kidneys, and adrenal glands of rats made hypertensive by ligation of the aorta between the renal arteries. We also measured renin mRNA in the kidneys of these renal hypertensive rats. The early phase of hypertension (day 6) was associated with significant increases in plasma renin activity and levels of circulating angiotensin II. The circulating renin-angiotensin system was not activated in the later phase of hypertension (day 24). Angiotensinogen mRNA levels were elevated in the lower brain stem of hypertensive rats at both stages of hypertension. In contrast, angiotensinogen mRNA levels in the hypothalamus were increased only at day 6 after aortic ligation. Decreased levels of angiotensinogen mRNA were observed in the cerebellum in both the early and later phases of the hypertension. Angiotensinogen mRNA levels in the adrenal gland below the ligature fell in the early phases but rose in the later phases of hypertension. Renin mRNA levels of the ischemic kidney remained elevated at both the early and later phases, whereas in both ischemic and nonischemic kidneys, levels of angiotensinogen mRNA remained below sham values throughout the period of study. These results indicate differential expression of renin-angiotensin system mRNAs in tissues of renal hypertensive rats. The differential changes in the expression of angiotensinogen mRNA over the course of development and maintenance of renal hypertension suggest that factors in addition to angiotensin II are important in modulating the expression of renin-angiotensin system genes.

Adrenal Glands↗
PubMed1992

Effects of opioids on vasoresponsiveness of porcine coronary artery.

Myocardial ischemia during surgery can be caused by coronary vasospasm. Neurohumoral mechanisms are involved in this phenomenon, and various substances have been suggested as possible causes, including acetylcholine, histamine, and norepinephrine. The responses of isolated porcine coronary arteries (from 117 pig hearts) with (E+) and without (E-) endothelium to these agents were investigated in the presence of fentanyl, sufentanil, and morphine. Fentanyl significantly shifted to the right, in a concentration-dependent fashion, the concentration-response curve to acetylcholine. This effect was not different between E+ and E- rings. Neither sufentanil nor morphine altered acetylcholine-induced contraction of porcine coronary arteries. Naloxone did not antagonize the suppressive effect of fentanyl on acetylcholine-induced contraction. The response of porcine coronary arteries to norepinephrine was decreased only at very high concentrations of fentanyl. Neither sufentanil nor morphine altered norepinephrine-induced contraction of porcine coronary arteries. Fentanyl, sufentanil, and morphine had no effect on histamine-induced contraction. We conclude that fentanyl antagonized acetylcholine-induced contraction of porcine coronary arteries. This effect of fentanyl seems to be caused by a direct effect on smooth muscle cells and is not opioid-receptor mediated.

Acetylcholine↗
PubMed1992

Patterns of renal function in hypertension due to unilateral renal artery occlusion.

We performed renal function studies in dogs with chronic renovascular hypertension produced by complete occlusion of a renal artery. In addition, we evaluated in anesthetized dogs the acute effects of a novel angiotensin converting enzyme inhibitor, CGS 16,617, on renal function and plasma neurohormones (epinephrine, norepinephrine and vasopressin) 4 weeks after initiation of 2 kidney, 1 clip hypertension. CGS 16,617 effectively decreased blood pressure in renal hypertensive animals. This response was associated with suppression of angiotensin II indicating effective converting enzyme inhibition. In the non-clipped kidney, acute administration of CGS 16,617 increased effective renal plasma flow but not glomerular filtration rate and urinary sodium excretion. In the clipped kidney, CGS 16,617 caused no change in any parameter of renal function. Plasma norepinephrine, epinephrine and vasopressin were unaffected by administration of CGS 16,617. These studies showed that chronic occlusion of a renal artery does not result in renal infarction because of a compensatory increase in the amount of blood provided through capsular collateral vessels. The collateral circulation which has developed in the clipped kidney explains the lack of a converting enzyme inhibitor effect.

Angiotensin-Converting Enzyme Inhibitors↗