Search PubMed⌕ Search

Biomedical subjects

R Veelken

Publications and source records attributed to R Veelken.

54 records · Page 3Linked to original sources
PubMed1993

Vascular conversion of angiotensin I in stroke-prone spontaneously hypertensive and Wistar-Kyoto rats.

OBJECTIVE: Linkage studies have shown that the gene locus for angiotensin converting enzyme (ACE) is associated with the expression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). We tested the hypothesis that the conversion of angiotensin I (Ang I) to angiotensin II (Ang II) in blood vessels is elevated in SHRSP. DESIGN: We measured the conversion rate of Ang I to Ang II during one pass through an isolated resistance vessel bed. We used the same substrains of SHRSP and Wistar-Kyoto control rats (WKY) that had been employed in the earlier linkage studies. METHODS: Isolated hindquarters from young and adult (10- to 12- and 36- to 38-week-old) rats were perfused with an artificial medium and then infused with Ang I at 0.5 and 2 pmol/ml. Ang I and II were measured with high-performance liquid chromatography and radioimmunoassay in hindquarter effluent and in blank control channels. Conversion and extraction rates were calculated from angiotensin levels in hindquarter and blank perfusion channels, respectively. RESULTS: The conversion rates of Ang I to Ang II did not differ between SHRSP and WKY in young or in adult rats. Captopril completely abolished the formation of Ang II in all groups of rats. During infusion at the higher dose of Ang I, the extraction of Ang I was significantly decreased in SHRSP compared with WKY. CONCLUSIONS: Our results are consistent with the notion that the metabolism of angiotensin is decreased in spontaneously hypertensive rats. However, we found no support for the hypothesis that vascular ACE is responsible for high blood pressure in SHRSP. These findings suggest that other genes close to the ACE locus or the hyperexpression of the enzyme in other areas may contribute to hypertension in these rats.

Aging↗
PubMed1993

A highly selective cardiorenal serotonergic 5-HT3-mediated reflex in rats.

To elucidate whether prolonged stimulation of cardiopulmonary serotonergic (5-HT3) receptors could play a role in the control of renal sympathetic nerve activity (RSNA), we compared 15-min intravenous infusions to bolus administrations of the 5-HT3 receptor agonist phenyl biguanide (PBG) and to a 0.9% saline load (5% body wt) in rats. Short-term and prolonged stimulation of 5-HT3-sensitive cardiopulmonary reflexes caused dose-related decreases in RSNA but not in lumbar sympathetic nerve activity (LSNA); only short-term stimulation caused decreases in blood pressure (BP) and heart rate (HR). Saline loading lowered RSNA but not LSNA, BP, or HR. Baroreceptor denervation did not influence any of these responses. Scopolamine attenuated BP and HR but not RSNA responses to bolus PBG. Pretreatment with a 5-HT3 receptor antagonist inhibited responses to PBG but not to saline. Vagotomy abolished all responses to all interventions. Thus 1) the prolonged stimulation of cardiopulmonary 5-HT3 receptors caused sustained suppression of RSNA, 2) decreased BP and HR were manifest only during short-term stimulation (3 min), and 3) blockade of 5-HT3 receptors did not influence responses to cardiopulmonary mechanoreceptor stimulation.

Animals↗
PubMed1993

Angiotensin II facilitates sympathetic transmission in rat hind limb circulation.

We developed a novel method to stimulate the sympathetic innervation of the isolated, perfused rat hind limb to investigate whether a subpressor concentration of angiotensin II (Ang II) facilitates noradrenergic transmission in the vascular bed to skeletal muscle. We electrically stimulated the lumbar sympathetic trunk while perfusing the preparation with artificial medium. Seventy-five percent of the resulting frequency-dependent increases in perfusion pressure were mediated by alpha 1-adrenergic receptors. Ang II (10 nM) significantly enhanced the effects of nerve stimulation at 1 and 10 Hz (by 42% and 35%, respectively). At a supramaximal stimulation frequency (20 Hz), Ang II prolonged the duration of the response without changing the peak increase in pressure. The reuptake inhibitor cocaine did not influence the effects of Ang II at 1 and 10 Hz but blocked the effect at 20 Hz. To control for nonspecific synergism with norepinephrine, we compared Ang II with vasopressin. Both peptides potentiated the pressor response to exogenous norepinephrine; however, vasopressin did not change the pressor response to nerve stimulation at any frequency. We conclude that Ang II, but not vasopressin, facilitates noradrenergic transmission in skeletal muscle resistance vessels, independent of its direct vasoconstrictor activity. The neurovascular preparation we describe may be useful in addressing other hypotheses concerning sympathetic transmission in skeletal muscle resistance vessels.

Angiotensin II↗
PubMed1993

Angiotensinogen is cleaved to angiotensin in isolated rat blood vessels.

The cleavage of synthetic tetradecapeptide renin substrate has been used to infer the presence of renin in the walls of isolated blood vessels; however, the conversion of natural angiotensinogen to angiotensin in isolated blood vessels has not been reported. We studied the release of angiotensinogen and the formation of angiotensins in a bloodless, perfused, isolated hind limb preparation of the rat. Perfusion with a modified Tyrode's solution resulted in spontaneous release of 4.7 +/- 1.5 pmol per 30 minutes of angiotensinogen as measured directly by radioimmunoassay. Western blot further identified the released material as angiotensinogen. Spontaneous release of angiotensins I and II was demonstrated by high performance liquid chromatography and radioimmunoassay. When highly purified rat angiotensinogen was added to the perfusate, release of angiotensin II was increased 14-fold compared with saline infusion. Captopril (10 mumol/L) inhibited angiotensinogen-induced angiotensin II release by 67% and led to an increase in angiotensin I release by 301%. Bilateral nephrectomy 24 hours before the experiments reduced basal angiotensin release below the detection limit and blunted angiotensinogen-induced angiotensin II formation by 95%. We conclude that active renin is present in the vessel wall and interacts with its natural substrate to form angiotensin peptides. Our data support the notion that the bulk of vascular renin is taken up from the circulation.

Angiotensin I↗
PubMed1993

Early interstitial changes in hypertension-induced renal injury.

To elucidate the mechanisms of hypertensive renal injury, we investigated the time course and extent of changes in matrix composition, as well as cell proliferation and infiltration in two-kidney, one clip rats. The nonclipped kidneys from hypertensive and sham-operated control rats (n = 5 to 10 in each group) were studied at 7, 14, 21, and 28 days after clipping. Systolic blood pressure was elevated by day 7 (154 +/- 3 versus 111 +/- 4 mm Hg in sham group, P < .001, n = 10 each). Hypertension resulted in an early expansion of the interstitial volume by 37%, whereas hypertensive vascular changes and glomerular injury did not become evident until day 21. Immunofluorescence studies revealed an early interstitial accumulation of collagens I, III, IV, V, VI, and fibronectin by day 7. In contrast, the glomeruli showed a mild to moderate increase in collagens I, III, IV, V, laminin, and fibronectin but not collagen VI later in the established phase of hypertension. Staining for proliferating cell nuclear antigen as a marker of cell replication was increased in tubular epithelial but not interstitial or glomerular cells. A progressive infiltration of macrophages (16 +/- 2 versus 9 +/- 1 ED1+ cells/mm2, P < .05, n = 6) and T lymphocytes (93 +/- 15 versus 74 +/- 7 CD4+ cells/mm2, n = 8) in the cortical interstitium had already occurred by day 7. On the other hand, only macrophages increased in number within the glomeruli. Thus, renovascular hypertension leads to an early tubular cell proliferation, mononuclear cell recruitment, and deposition of matrix proteins primarily within the interstitium. We conclude that the injury producing nephrosclerosis in this model extends far beyond the glomeruli. Both the tubules and the interstitium are actively involved and may be the more important initial sites of injury.

Animals↗
PubMed1992

Increased vascular angiotensin formation in female rats harboring the mouse Ren-2 gene.

Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin activity. We tested the hypothesis that these rats exhibit an increase in vascular angiotensin formation caused by the presence of the transgene. We measured the release of angiotensins I and II from isolated perfused hindquarters by high-performance liquid chromatography and radioimmunoassay. Female rats heterozygous for the transgene had significantly elevated mean arterial pressure compared with control rats (189.3 +/- 9.5 versus 110.0 +/- 5.4 mm Hg, p less than 0.05). Plasma angiotensin II was significantly decreased in transgenic rats. Transgenic rat hindquarters released more angiotensin I (121 +/- 37 versus 39 +/- 12 fmol/30 min, n = 7 each) and more angiotensin II (210 +/- 21 versus 62 +/- 12 fmol/30 min, p less than 0.05, n = 7 each) than control rat hindquarters. Captopril increased angiotensin I release and decreased angiotensin II values in both transgenic and control rat hindquarters. Bilateral nephrectomy 24 hours before hindquarter perfusion greatly reduced angiotensin release from control rat hindquarters but not from transgenic rat hind limbs. We also tested for the presence of Ren-2 messenger RNA in mesenteric and aortic tissue by RNase protection assay and Northern blot analysis. We found that Ren-2 messenger RNA was present in mesenteric and aortic tissue of transgenic but not of control rats. We conclude that the Ren-2 transgene is expressed in vascular tissue of transgenic rats and may be responsible for substantial increases in vascular angiotensin formation.

Angiotensin II↗
PubMed1992

Effect of antihypertensive therapy on the progression of non-diabetic renal disease.

There is a clear, inverse association between the level of blood pressure and the progression of renal disease. This association appears to extend well within the "normotensive" blood pressure range. Currently, there are no absolutely incontrovertible data from prospective, randomized trials in humans documenting that high blood pressure is the cause of an accelerated loss of GFR, or that the loss in renal function can be prevented by lowering blood pressure below 140/90 mmHg. Nevertheless, an aggressive lowering of blood pressure in patients with hypertension and renal disease seems reasonable and desirable. First, the control of blood pressure lowers the "all causes" risk of cardiovascular morbidity and mortality in all patients with elevated blood pressure. Second, any detrimental effects on GFR are uncommon or transient in these patients. Third, the beneficial effects on GFR are firmly supported in animal studies and in humans with malignant hypertension. Fourth, a growing body of evidence from human trials supports the inverse correlation between blood pressure and decrease in GFR, even below a level of 140/90 mmHg. The evidence for these conclusions is reviewed.

Antihypertensive Agents↗
PubMed1990

Improved methods for baroreceptor investigations in chronically instrumented rats.

We developed a novel approach using inflatable cuffs in order to test the baroreceptor reflex in conscious rats. The cuffs we employed differ from previous approaches in which cuffs are implanted in the thorax. Instead, we placed cuffs around the abdominal aorta and vena cava immediately below the diaphragm. We assessed the utility of this approach in several ways. First, we found that implantation could be accomplished without the stress associated with opening the thoracic cavity. Functioning preparations were far easier to obtain compared to the thoracic approach. The thoracic approach using two-vessel constriction resulted in inordinant mortality and failed preparations. We found that blood pressure changes could be easily exerted over a considerable range in conscious animals with the abdominal cuffs. For instance, blood pressure could be easily manipulated over a range of 100 mmHg (increased or decreased by 50 mmHg from baseline). This simpler and more reliable approach will facilitate baroreceptor investigations in conscious rats.

Animals↗
PubMed1990

Epicardial serotonin receptors in circulatory control in conscious Sprague-Dawley rats.

To investigate cardiac chemoreceptors in rats a catheter was chronically implanted into the pericardial sac via the thymus. Intrapericardial (ipc) injection of 200 microliters isotonic saline vehicle did not alter arterial blood pressure, heart rate, right atrial pressure, or respiratory rate. Phenyl biguanide (PBG) and nicotine (NIC) were injected into the pericardial sac. In intact rats anesthetized with methohexital sodium, 90 micrograms PBG ipc decreased blood pressure (BP), heart rate (HR), and renal nerve activity (RNA), whereas 300 micrograms NIC ipc increased BP and decreased HR and RNA. Sinoaortic baroreceptor denervation (SAD) did not affect the responses to PBG and abolished only the HR response to NIC. When vagotomy was added to SAD, all responses to intrapericardial PBG were abolished, but the increase in BP and decrease in RNA resulting from intrapericardial NIC persisted. In SAD rats anesthetized with methohexital, PBG produced dose-dependent decreases in BP and RNA, whereas NIC produced dose-dependent increases in BP and decreases in RNA; the serotonin (5-HT3) antagonist MDL 72222 (80 micrograms ipc) abolished the responses to PBG but not to NIC. MDL 72222 inhibited BP and RNA responses to PBG to a similar extent in conscious and anesthetized SAD rats. Anesthesia attenuated the magnitude and time course of BP and RNA responses to PBG compared with the conscious state. In conclusion, 1) sympathoinhibitory responses to intrapericardial PBG and NIC are mediated by epicardial receptors with different afferent neural pathways, PBG by cardiac vagal afferents and NIC by nonvagal, possibly cardiac sympathetic afferents; 2) PBG exerts its effects via epicardial 5-HT3 receptors; 3) anesthesia attenuates the responses to PBG.

Animals↗
PubMed1989

Effects of intravenous AVP on cardiac output, mesenteric hemodynamics, and splanchnic nerve activity.

To elucidate the effects of intravenous arginine vasopressin (AVP) on the neural control of the circulation, we investigated the action of AVP on neural circulatory control with respect to its influence on cardiac output (CO), mesenteric blood flow (MBF), and splanchnic nerve activity (SpNA) in conscious rats. We implanted Doppler flow probes and bipolar electrodes into seven Wistar rats for continuous monitoring of CO, MBF, and SpNa. After the infusion of four different equipressor doses of AVP and methoxamine, the decreases in heart rate (HR) and CO were significantly greater with AVP than with methoxamine. Pretreatment with atenolol and methscopolamine bromide abolished the decreases in HR after both AVP and methoxamine injections but attenuated the AVP-induced decreases in CO less than the methoxamine-induced CO decreases. In untreated rats and in rats receiving cardiac autonomic blockade, the reduction in MBF and the increases in mesenteric resistance were greater after AVP than after methoxamine. Furthermore, SpNA decreased to a greater extent with all doses of AVP than with methoxamine. We conclude that in the rat the exaggerated reduction in CO induced by circulating AVP is not because of a sensitization of neural mechanisms but rather to caridac actions of the peptide. In contrast, AVP sensitizes the sympathetic control of the mesenteric vascular bed to counterbalance its potent local vasoconstrictor effects.

Animals↗
PubMed1989

Dissociation of renal nerve and excretory responses to volume expansion in prehypertensive Dahl salt-sensitive and Dahl salt-resistant rats.

Prehypertensive Dahl salt-sensitive rats on low sodium diet have impaired baroreceptor and cardiopulmonary receptor function as compared with Dahl salt-resistant control rats. We tested whether these abnormalities influenced the ability of conscious prehypertensive Dahl salt-sensitive rats to excrete a moderate intravenous isotonic saline volume load (0.9% NaCl, 3% body weight i.v.). During control, 30-minute volume expansion, and 2-hour recovery periods, arterial blood pressure and heart rate did not change. Glomerular filtration rate and renal plasma flow remained stable throughout control and recovery. The amount of the volume load excreted as either water or sodium was the same for Dahl salt-sensitive and Dahl salt-resistant rats with either denervated or innervated kidneys. The time course of water and sodium excretion was similar in Dahl salt-sensitive and Dahl salt-resistant rats. Renal sympathetic nerve activity, however, showed different patterns. Although the initial decrease in renal sympathetic nerve activity during volume expansion was similar for both groups, Dahl salt-sensitive rats exhibited a prompt return of renal sympathetic nerve activity to control levels, whereas renal sympathetic nerve activity in Dahl salt-resistant rats remained decreased throughout the recovery period. The rapid recovery of renal sympathetic nerve activity to control levels after volume expansion in Dahl salt-sensitive rats supports the concept of impaired cardiopulmonary receptor function in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

An approach to measuring cardiac output with Doppler flow probes in conscious rats.

The continuous measurement of cardiac output in conscious rats is difficult. Previously, Doppler flow probes have been applied to the ascending aorta by means of silicone cuffs. The placement of these cuffs can conceivably introduce errors engendered by the destruction of nerve fibers that are important in cardiac autonomic innervation. We report a novel method of Doppler flow-probe attachment directly to the ascending aorta by means of a polyacrylic cement. When we compared the response with baroreceptor activation with methoxamine and nitroprusside in conscious rats equipped either with probes attached via cuffs or directly via cement, we observed that animals equipped with cuffs failed to give the expected cardiac output and heart rate responses after nitroprusside administration. In contrast, animals that had their probes attached with cement displayed the expected responses. The data not only show that probes applied with cement give a result superior to probes attached with cuffs but also verify the suspicion that the ascending aorta is associated with nerve fibers that are important in mediating baroreceptor responses.

Animals↗
PubMed1988

Substance P induces a cardiovascular defense reaction in the rat: pharmacological characterization.

In this study in conscious rats, we tested the hypothesis that substance P, a central pressor peptide and a potential transmitter substance of pain pathways, could be involved in the cardiovascular defense reaction that is typically associated with unpleasant sensory stimuli. The hemodynamic responses to centrally administered substance P were pharmacologically characterized. The increases in blood pressure and heart rate after intracerebroventricular injections of substance P were accompanied by mesenteric and renal vasoconstriction and hind limb vasodilation (pulsed-Doppler flow probes). The pressor and vasoconstrictor responses were attenuated by peripheral alpha 1-adrenoceptor blockade with prazosin but were not influenced by blockade of vascular vasopressin receptors with d(CH2)5Tyr(Me) arginine vasopressin (AVP). Cardiac beta 1-adrenoceptor blockade with metoprolol abolished the tachycardic and reduced the pressor responses. Substance P-induced hind limb vasodilation was not sensitive to intravenous atropine but was largely prevented by peripheral beta 2-adrenoceptor blockade with ICI 118,551. Thus, the substance P-induced pressor effects are mediated by alpha 1-adrenergic sympathetic vasoconstriction and beta 1-adrenergic cardiac stimulation, whereas the hind limb vasodilation is mainly due to beta 2-adrenergic stimulation. Substance P dose-dependently (0.01-10 micrograms i.c.v.) released oxytocin but not vasopressin or adrenocorticotropic hormone (ACTH) from the pituitary gland. High doses reduced basal ACTH levels. Together with the hemodynamic responses, a behavioral arousal reaction was observed, which included increased locomotion, grooming, scratching, and skin biting. Our results demonstrate that a neuropeptide can induce classic cardiovascular defense reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1987

Dissociation between heart rate and sympathetic nerve responses to baroreceptor activation in spontaneously hypertensive rats.

We tested the baroreflex in conscious, stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto controls (WKY) with incremental bolus injections of nitroprusside and methoxamine. The change in heart rate (HR) per change in mean blood pressure (MAP) was greater in WKY than in SHRSP. In contrast, the change in splanchnic nerve activity (SpNA) per change in MAP was greater in SHRSP than in WKY. The sympathetic outflow in SHRSP seems more reactive to blood pressure changes than in WKY. The discordance in HR and SpNA changes suggests that the integration of autonomic function in SHRSP is impaired.

Animals↗
PubMed1986

Atrial natriuretic factor determinations and chronic sodium homeostasis.

To examine the physiological role of atrial natriuretic factor (ANF) in the maintenance of sodium homeostasis under various conditions, we performed experiments in rats across a wide range of sodium intake, in rats with chronic renal insufficiency at extremes of sodium intake, and in rats given desoxycorticosterone acetate. After three weeks of a very low sodium diet, regular diet, or regular diet plus 1% saline as drinking water, no difference in plasma values of immunoreactive atrial natriuretic factor (IR-ANF) were identified, while rats at the lowest level of sodium intake had elevated atrial values. Normal rats, and rats with 5/6 nephrectomy has plasma values of IR-ANF which were no different irrespective of their sodium intake, nor were atrial values in these rats different. Although mineralocorticoid "escape" could be documented by changes in urine sodium excretion, neither plasma nor atrial IR-ANF values showed differences either at 24 or 72 hr after "escape". The data are consistent with previous observations that ANF serves the purpose of affecting rapid adjustments to large alterations in circulating fluid volume. Chronic high sodium intake, adaptation to renal insufficiency, and adjustment to the effect of mineralocorticoid do not appear to be associated with increased circulating plasma concentrations of IR-ANF.

Animals↗
PubMed1986

Effect of urapidil, clonidine, and prazosin on sympathetic tone in conscious rats.

To test the hypothesis that the hypotensive action of urapidil is in part related to a direct action on the brain, the central (intracerebroventricular) and peripheral (intravenous) effects of urapidil were studied and compared with those obtained with clonidine and prazosin. All studies were conducted in conscious, chronically instrumented stroke-prone spontaneously hypertensive rats (SHRSP). Efferent sympathetic nervous system activity was estimated by means of a bipolar electrode implanted on the splanchnic nerve. Only clonidine, administered intracerebroventricularly and intravenously, decreased sympathetic nerve activity. Urapidil and prazosin either did not affect sympathetic nerve activity after central administration or increased it after peripheral administration at low and high doses, respectively. Centrally administered urapidil and prazosin lowered blood pressure but also blocked the response to intravenously administered phenylephrine; this result suggests a peripheral effect. Centrally administered urapidil decreased heart rate. Urapidil given either intracerebroventricularly or into the cisterna magna had no influence on baroreceptor responses. Intravenous infusions of urapidil and prazosin in sufficient doses to lower blood pressure in spontaneously hypertensive rats by 50 mm Hg completely blocked the actions of phenylephrine. These data suggest that in conscious SHRSP urapidil lowers blood pressure through peripheral blockade of alpha 1-adrenergic receptors rather than by means of central sympathetic suppression. In this regard urapidil resembles prazosin rather than clonidine; however, the effect of urapidil on heart rate is consistent with a central mode of action.

Animals↗
PubMedDate not supplied

A new method for collecting urine directly from the ureter in conscious unrestrained rats.

We have developed a new method for urine collection in conscious, unrestrained rats through a chronic indwelling ureteral catheter, which allows direct differential sampling of small urine fractions over periods as small as 1 min. The technique was validated in intact and unilaterally nephrectomized rats by cumulative intravenous saline loading. Comparison of kidney with ureter catheter and contralateral kidney (urine collection from the bladder) revealed no differences in glomerular filtration rate and urine production between both kidneys. One week after catheter implantation in unilaterally nephrectomized rats, signs of renal functional disturbance as assessed by glomerular filtration rate, urine concentrating capacity after 24 h water deprivation, and plasma and urinary urea concentrations before and after water deprivation were not detected. Our technique provides a novel tool for direct measurements of short-term changes in urine composition in conscious animals.

Animals↗