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P Boer

Publications and source records attributed to P Boer.

At least 19 recordsLinked to original sources
PubMed2004

Disparate systemic and renal blocking properties of angiotensin II antagonists during exogenous angiotensin II administration: implications for treatment.

Generation of angiotensin II (Ang II) contributes to the pathogenesis of cardiovascular diseases. Owing to the existence of high levels of Ang II within the kidney, blockade of the intrarenal Ang II levels may be important since long term outcome seems not only to be related to blood pressure per se. This was a prospective, randomized, double-blind, placebo-controlled study, with crossover design. We examined in 13 patients with mild to moderate hypertension the specific systemic and renal blocking properties of two different Ang II receptor blockers during a wide range of Ang II concentrations, 24 h post dose. The effects were evaluated after 4 weeks treatment with candesartan cilexetil (16 mg OD), losartan (50 mg OD) and placebo using clearance techniques. Candesartan reduced the 24 h blood pressure better than losartan (138(*)/87+/-12/8 vs 145/89+/-12/7 mmHg, (*)P<0.05 vs losartan) and placebo. Despite the lower blood pressure, candesartan attenuated the Ang II-induced response on ERPF and RVR markedly better than losartan or placebo. The GFR decreased, as expected, with placebo, but remained stable with candesartan. The present study demonstrates that in hypertensive patients candesartan and to a lesser degree losartan are effective in blocking the systemic and renal effects of Ang II during a wide range of Ang II infusion rates. Interestingly, 24 h post dose, candesartan effectively diminished the change in ERPF as well as GFR. This sustained renal effect of candesartan may be of importance, especially in pathophysiological circumstances in which (high renal levels of) Ang II contributes to cardiovascular damage.

Adult↗
PubMed2003

Plasma aldosterone concentrations and plasma renin activity in healthy dogs and dogs with hyperadrenocorticism.

The mean (se) basal plasma aldosterone concentrations were significantly lower in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH) (75 [9] pmol/litre) than in 12 healthy dogs (118 [14] pmol/litre), whereas in five dogs with hyperadrenocorticism due to an adrenocortical tumour they were significantly higher (205 [109] pmol/litre). The mean basal renin activity was not significantly different between the dogs with PDH (303 [48] fmol/litre/second), the dogs with an adrenocortical tumour (141 [63] fmol/litre/second), and the control dogs (201 [25] fmol/litre/second). At three and four hours after the intravenous administration of 0.1 mg/kg dexamethasone, the concentrations of aldosterone decreased significantly to about 60 per cent of their initial values in the control dogs but did not change in the dogs with PDH or an adrenocortical tumour. In the dogs with PDH the renin activity increased significantly after the administration of dexamethasone.

Adrenal Cortex Neoplasms↗
PubMed2002

Exercise-induced hyperkalemia in hypothyroid dogs.

We investigated the effect of hypothyroidism in dogs on (1) the Na+-, K+ -ATPase concentration in skeletal muscle, and (2) potassium (K+) homeostasis at rest and during exercise. Prior to and 1 year after induction of hypothyroidism by surgery and subsequent radiothyroidectomy, the Na+-, K+ -ATPase concentrations were quantified in biopsies of sternothyroid muscles of seven Beagle dogs by measuring [3H]ouabain binding capacity. In addition, plasma K+ concentrations were measured at rest and after treadmill exercise in six hypothyroid and seven euthyroid Beagle dogs. During hypothyroidism, the mean Na+ -, K+ -ATPase concentration in muscle biopsies was 41% lower than during euthyroidism. The mean resting plasma K+ value of the hypothyroid dogs was significantly (14%) higher than that of the euthyroid dogs. In the hypothyroid dogs, plasma K+ concentration increased significantly during exercise, whereas there was no rise in the euthyroid dogs. The rise in plasma K+ concentration could not be ascribed to muscle damage, as plasma creatine kinase concentrations remained within reference range. Also renal K+ retention was an unlikely explanation, as plasma aldosterone concentration and plasma renin activity rather increased than decreased during exercise. In conclusion, hypothyroid dogs tend to develop hyperkalemia during exercise, which for a large part can be explained by the severe reduction of the Na+ -, K+ -ATPase capacity in the skeletal muscle pool.

Aldosterone↗
PubMed2001

Decelerated rate of dendrite outgrowth from dopaminergic neurons in primary cultures from brains of hypoxanthine phosphoribosyltransferase-deficient knockout mice.

Lesch-Nyhan syndrome (LNS), caused by the complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT), is characterized by a neurological deficit, the etiology of which is still unclear. Evidence has accumulated indicating that it reflects dopamine deficiency associated with defective arborization of dopaminergic dendrites. We monitored the differentiation in vitro of dopaminergic neurons, cultured from HPRT-deficient knockout mice. The HPRT-deficient dopaminergic neurons exhibited a decelerated rate of outgrowth of dendrites in comparison to that of control neurons resulting, after 8 days in culture, in 32% smaller average total length of dendrites per neuron (P<0.025). The results suggest that the abnormal dendrite outgrowth in LNS reflects a defective developmental process.

Animals↗
PubMed2001

Aldosteronoma in a dog with polyuria as the leading symptom.

In a 10-year-old castrated male shorthaired German pointer polyuria was associated with slight hypokalemia, hypophosphatemia and alkalosis, as well as elevated plasma concentrations of a glucocorticoid-inducible iso-enzyme of alkaline phosphatase. Repeated measurements of urinary corticoids and normal suppressibility of the hypothalamus-pituitary-adrenocorticial axis excluded glucocorticoid excess. Urine osmolality (Uosm) did not increase during administration of the vasopressin analogue desmopressin. At the time water deprivation had caused Uosm to rise from 300 to 788 mOsm/kg, there was also plasma hypertonicity. During hypertonic saline infusion the osmotic threshold for vasopressin release was increased. The combination of elevated plasma aldosterone concentrations and unmeasurably low plasma renin activity pointed to primary hyperaldosteronism. As initially computed tomography (CT) did not reveal an adrenocortical lesion, the dog was treated with the aldosterone antagonist spironolactone. This caused Uosm to rise in a dose-dependent manner. However, well-concentrated urine was only achieved with doses that gave rise to adverse effects. Once repeated CT, using 2-mm-thick slices, had revealed a small nodule in the cranial pole of the left adrenal, unilateral adrenalectomy was performed which resolved the polyuria completely. Also the plasma concentrations of kalium, aldosterone and renin activity returned to within their respective reference ranges. The adrenocortical nodule had the histological characteristics of an aldosteronoma, with the non-affected zona glomerulosa being atrophic.In this dog with primary hyperaldosteronism the polyuria was characterized by vasopressin resistance and increased osmotic threshold of vasopressin release, similar to the polyuria of glucocorticoid excess. The possibility is discussed that the polyuria of glucocorticoid excess is actually a mineralocorticoid effect.

Adrenalectomy↗
PubMed2001

Hyperaldosteronism in a cat with metastasised adrenocortical tumour.

In a 12-year-old male shorthaired cat with attacks of hypokalaemic muscular weakness in spite of oral potassium supplementation, highly elevated plasma aldosterone concentrations in combination with low plasma renin activity pointed to primary hyperaldosteronism. Ultrasonography and computed tomography revealed a large left-sided adrenal tumour growing into the phrenicoabdominal vein and the caudal vena cava. The tumour and its intravascular extension were surgically removed, but the subsequent stenosis of the caudal vena cava caused congestion and renal failure. At autopsy pulmonary micrometastases of the aldosteronoma were found.

Adrenal Cortex Neoplasms↗
PubMed2000

Unchanged cardiac angiotensin II levels accompany losartan-sensitive cardiac injury due to nitric oxide synthase inhibition.

Chronic nitric oxide synthase (NOS) inhibition results in hypertension and myocardial injury. In a rapid and severe model of chronic NOS inhibition, we determined the role of angiotensin II in these effects by using angiotensin II receptor blockade and by measuring cardiac angiotensin II concentrations before and during development of cardiac damage. Rats received either no treatment, the NOS inhibitor Nomega-nitro-L-arginine (L-NNA; 500 mg/l), the angiotensin AT(1) receptor antagonist losartan (400 mg/kg chow), or L-NNA plus losartan for 21 days. In the second protocol, five groups of rats received L-NNA (500 mg/l) for 0, 4, 7, 14 and 21 days, respectively. L-NNA increased systolic blood pressure (SBP) (227+/-8 versus 143+/-6 mm Hg; P<0.01), heart weight index (0.44+/-0.02 versus 0.32+/-0.01; P<0.01) and induced coronary vasculitis and myocardial necrosis. Co-treatment with losartan prevented all changes. L-NNA during 4 days decreased cardiac angiotensin II (23+/-4 versus 61+/-15 fmol/g; P<0.05). Although after 7 days, fresh infarcts and after 14 days organized infarcts were present, cardiac angiotensin II was only slightly increased after 21 days (100+/-10 fmol/g; P<0.05). In conclusion, losartan-sensitive cardiac damage due to chronic NOS inhibition is not associated with primary increase of cardiac angiotensin II, suggesting that chronic NOS inhibition increases cardiac sensitivity for angiotensin II.

Angiotensin II↗
PubMed2000

Folic acid reverts dysfunction of endothelial nitric oxide synthase.

5-methyltetrahydrofolate (MTHF), the active form of folic acid, has been reported to restore NO status in hypercholesterolemic patients. The mechanism of this effect remains to be established. We assessed the effects of L- and D-MTHF on tetrahydrobiopterin (BH(4))-free and partially BH(4)-repleted endothelial NO synthase (eNOS). Superoxide production of eNOS and the rate constants for trapping of superoxide by MTHF were determined with electron paramagnetic resonance using 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO) as spin trap for superoxide. NO production was measured with [(3)H]arginine-citrulline conversion or nitrite assay. The rate constants for scavenging of superoxide by L- and D-MTHF were similar, 1.4 x 10(4) ms(-1). In BH(4)-free eNOS, L- and D-MTHF have no effect on enzymatic activity. In contrast, in partially BH(4)-repleted eNOS, we observe a 2-fold effect of MTHF on the enzymatic activity. First, superoxide production is reduced. Second, NO production is enhanced. In cultured endothelial cells, a similar enhancement of NO production is induced by MTHF. In the present study, we show direct effects of MTHF on the enzymatic activity of NO synthase both in recombinant eNOS as well as in cultured endothelial cells, which provides a plausible explanation for the previously reported positive effects of MTHF on NO status in vivo.

Cells, Cultured↗
PubMed2000

Conversion to mycophenolate mofetil in conjunction with stepwise withdrawal of cyclosporine in stable renal transplant recipients.

BACKGROUND: Mycophenolate mofetil (MMF) is now part of standard immunosuppression in the first phase after renal transplantation. A relevant question is if it can replace drugs such as cyclosporine (CsA) in the maintenance treatment, improving cardiovascular risk profile. METHODS: In 17 patients with a stable renal function (at least 6 months) posttransplantation, we studied the effect of CsA replacement by MMF. After starting MMF (1 g b.i.d.), CsA dosage was reduced from regular to low (median trough level 130 microg/L, respectively, 45 microg/L), followed by complete withdrawal, while prednisone (7.5 mg daily) was continued. We measured ambulatory blood pressure, glomerular filtration rate, renal plasma flow, renal vascular resistance, and metabolic factors at start and after 8 weeks on regular, low-dose CsA, respectively, no CsA with MMF and prednisone. RESULTS: Two patients dropped out after the switch to low-dose CsA/MMF, due to diarrhea in one and a steroid responsive rejection in the other. The complete switch from CsA to MMF was successful in all 15 patients and accompanied by a decrease in 24 hr systolic blood pressure (from 152+/-13 to 145+/-13 mmHg; P<0.01), diastolic blood pressure (93+/-9 to 89+/-12 mmHg; P<0.05), RVR (0.29+/-0.06 to 0.25+/-0.09 mmHg.ml/min; P<0.05), and an increase in glomerular filtration rate (46.6+/-8.8 to 58.0+/-10.5 ml/min; P<0.01) and renal plasma flow. Intermediate low density lipoprotein-cholesterol decreased (0.79+/-0.37 to 0.41+/-0.16 mmol/L; P<0.01). High density lipoprotein-cholesterol decreased, but remained in the safe range. After 1 year two patients stopped the MMF; one because of Kaposi's sarcoma and one because of recurrent infections CONCLUSIONS: The stepwise switch from CsA to MMF was safe and mostly successful, and had beneficial effects on blood pressure, glomerular hemodynamics, and lipid profile. Beneficial trends were already present after partial withdrawal of CsA.

Adult↗
PubMed1999

Losartan-sensitive renal damage caused by chronic NOS inhibition does not involve increased renal angiotensin II concentrations.

BACKGROUND: Chronic nitric oxide synthase (NOS) inhibition results in hypertension, proteinuria, and renal morphological changes. Continuous angiotensin II (Ang II) blockade prevents these effects, suggesting an essential role of Ang II. However, it is not known whether renal Ang II concentrations are primarily increased or whether the scarcity of NO allows normal concentrations of Ang II to cause these detrimental effects. Therefore, we measured renal Ang II concentrations before and during the development of renal damage. METHODS: Group 1 served as controls. Groups 2 through 5 received the NOS inhibitor Nomega-nitro-L-arginine (L-NNA; 40 mg/kg/day) for 4, 7, 14, and 21 days, respectively. Systolic blood pressure (SBP), proteinuria, glomerular filtration rate (GFR), and renal and blood Ang II were measured. In a separate experiment, rats were treated with L-NNA + the Ang II AT1 receptor blocker losartan to determine the functional effects of endogenous Ang II during chronic NOS inhibition. RESULTS: L-NNA treatment resulted in an increase in SBP from day 4 (161 +/- 4 vs. 135 +/- 4 mm Hg in control, P < 0.05) to day 21 (230 +/- 9 mm Hg). GFR was decreased from day 4 (1.9 +/- 0.2 vs. 2.5 +/- 0.2 ml/min in control, P < 0.05) to day 21 (1.2 +/- 0.2 ml/min). Proteinuria was increased from day 14 (85 +/- 14 vs. 6 +/- 1 mg/day in control, P < 0.05) to day 21 (226 +/- 30 mg/day). L-NNA treatment during four days resulted in a significant decrease in renal Ang II (183 +/- 32 vs. 454 +/- 40 fmol/g in control, P < 0.05). On day 7, 14, and 21, renal Ang II was not significantly different from the control. Blood Ang II was not significantly different from the control on days 4, 7, and 14 but was significantly increased after 21 days of L-NNA treatment (215 +/- 35 vs. 78 +/- 13 fmol/ml in control, P < 0.05). Ang II type-1 (AT1) receptor blockade prevented the severe renal injury and hypertension induced by chronic NOS inhibition. CONCLUSIONS: Losartan-sensitive renal damage caused by chronic NOS inhibition does not involve increased renal Ang II concentrations. This suggests that the detrimental effects of endogenous Ang II are increased during chronic NOS inhibition. Thus, when NO levels are low, normal Ang II concentrations can cause renal injury and hypertension.

Angiotensin II↗
PubMed1999

Nitric oxide production is reduced in patients with chronic renal failure.

In patients with chronic renal failure (CRF), atherosclerosis is a major cause of cardiovascular morbidity and mortality. Generally, atherosclerosis has been associated with a reduced bioavailability of nitric oxide (NO). Experimental studies have indicated the presence of enhanced NO degradation by reactive oxygen species as well as decreased NO production as possible causes for this reduced NO bioavailability. So far, the question whether or not NO production is impaired in patients with CRF has never been investigated. Therefore, we measured whole body NO production in 7 patients with CRF, and in 7 matched healthy subjects. To assess the relative importance of a dysfunction of NO synthase (NOS), we compared the NO production of these patients to that of 2 other groups known to have endothelial dysfunction, ie, 7 patients with familial hypercholesterolemia (FH) who did not yet have signs of clinical cardiovascular disease (all nonsmokers), and 5 cigarette smokers. These groups were also compared with 7 nonsmoking, age-matched healthy subjects. Whole body NO production, determined as in vivo arginine-to-citrulline conversion, was assessed by giving an intravenous infusion of [15N2]-arginine as a substrate for NOS and measuring isotopic plasma enrichment of [15N]-citrulline by LC-MS. NO production in the CRF patients (0.13+/-0.02 micromol. kg-1. h-1) was significantly lower (P<0.05) than in the corresponding control group (0.23+/-0.09 micromol. kg-1. h-1). NO production also tended to be lower in the FH patients (0.16+/-0.04 micromol. kg-1. h-1), but the difference with the corresponding control group did not reach significance (0.22+/-0.06 micromol. kg-1. h-1). In the group of smokers, NO production was similar to that in nonsmokers (0. 22+/-0.09 micromol. kg-1. h-1). In conclusion, it is demonstrated for the first time that basal whole body NO production is reduced in patients with CRF. This finding implies that therapeutic interventions to endothelial dysfunction in these patients should be primarily directed toward improvement of NO production. The finding of only a tendency toward reduction of NO production in patients with FH and the absence of a reduction in cigarette smokers suggests that other mechanisms such as enhanced NO degradation may be involved in the decrease of NO bioavailability in these groups.

Arginine↗
PubMed1999

Increased availability of nitric oxide leads to enhanced nitric oxide dependency of tubuloglomerular feedback in the contralateral kidney of rats with 2-kidney, 1-clip Goldblatt hypertension.

The contralateral kidney of 2-kidney, 1-clip hypertensive (2K1C) rats is unable to escape the renal vasoconstrictive and sodium-retaining effects of increased circulating angiotensin II levels. Evidence is accumulating that renal function is relatively preserved by enhanced influence of NO in the contralateral kidney. In this study, we investigated (1) whether the high NO dependency of renal hemodynamics in the contralateral kidney is due to increased availability of NO or increased sensitivity to NO and (2) whether elevated NO activity dampens the actions of angiotensin II to enhance tubuloglomerular feedback (TGF) responses in the nonclipped kidney of 2K1C rats. To estimate whether the available NO is increased, the NO clamp technique was applied in rats that underwent sham operation (n=6) and in the contralateral kidney of 2K1C Sprague-Dawley rats (3 weeks old; 0.25-mm silver clip; n=6). During systemic infusion of nitro-L-arginine (L-NNA; 50 microg/kg. min(-1)), sodium nitroprusside (SNP) was infused in the renal artery and the rate was adjusted so that renal vascular resistance (RVR) was restored to baseline levels. In sham rats, RVR increased during L-NNA treatment from 17.2+/-2.0 to 33.0+/-3.6 U (P<0.01) and was restored to baseline values during SNP infusion (17.1+/-2.3 U); 9. 2+/-1.8 nmol/min of SNP was needed to restore RVR to baseline values. In 2K1C rats, RVR increased during L-NNA treatment from 16.7+/-1.1 to 53.4+/-3.5 U (P<0.01). This increase of RVR was significantly larger than in sham rats. RVR was restored to baseline values during SNP infusion (17.4+/-0.9 U); 26.0+/-4.3 nmol/min of SNP was needed to restore RVR to baseline values (P<0.05 versus sham). Furthermore, maximum TGF responses were assessed before and during late proximal tubular infusion of L-NNA in the kidneys of sham rats and the nonclipped kidneys of 2K1C rats. Control maximum TGF responses were 4.7+/-0.7 and 5.1+/-0.4 mm Hg in sham and 2K1C rats, respectively. During intraluminal L-NNA infusion, maximum TGF responses were 15. 4+/-0.9 mm Hg in sham rats and 22.2+/-2.5 mm Hg in 2K1C rats (P<0.05 versus sham). Finally, urinary NO(2)+NO(3) excretion in the nonclipped kidney was significantly higher than in the clipped kidney (P<0.05). In conclusion, (1) as assessed using the NO clamp, ambient intrarenal NO levels are increased in the contralateral kidney of 2K1C rats and (2) the NO dependency of the TGF system is enhanced. These experiments indicate that adaptations in NO activity lead to relatively low TGF responsiveness, which will offset the simultaneous sodium-retaining actions of angiotensin II on proximal tubular reabsorption and TGF responsiveness.

Analysis of Variance↗
PubMed1998

Assessment of nitric oxide production by measurement of [15N]citrulline enrichment in human plasma using high-performance liquid chromatography-mass spectrometry.

Nitric oxide (NO) is formed by a class of NO synthases (NOS), which convert arginine into citrulline. A decreased in vivo NO availability can be the result of an increased NO inactivation or a decreased NO production. The latter can be assessed by measurement of isotopic enrichment of plasma citrulline during infusion of isotopically labeled arginine. The potential of high-performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) to determine enrichments of [15N2]arginine and [15N]-citrulline in plasma during infusion of [15N2]arginine in humans was investigated. Two types of MS instruments were evaluated: a sector-type mass spectrometer equipped with a frit fast-atom bombardment (FAB) interface and a quadrupole instrument with electrospray ionization (ESI). FAB-MS appeared to be unsuitable for determination of isotope ratios, because background ions influenced the observed isotope ratio in an unpredictable way. In combination with either off- or on-line reversed-phase HPLC, ESI-MS proved to be a more reliable technique. However, the amount of material that is introduced in the mass spectrometer is critical and should be carefully controlled. During infusion of [15N2]arginine in 14 healthy subjects, a mean arginine-to-citrulline conversion rate of 0.22 +/- 0.07 (SD) mumol.kg-1.h-1 was found. In 4 subjects who received an intravenous infusion with the NOS antagonist L-NMMA, the conversion rate decreased from 0.30 +/- 0.14 to 0.10 +/- 0.06 mumol.kg-1.h-1. It is concluded that ESI-MS in combination with HPLC can be successfully applied for determination of arginine and citrulline enrichments in plasma, thus providing a useful tool for assessment of in vivo NO production.

Chromatography, High Pressure Liquid↗
PubMed1998

Cyclic AMP decreases the availability of 5-phosphoribosyl-1-pyrophosphate and decelerates de novo purine synthesis in rat hepatocytes.

Cyclic adenosine monophosphate (cAMP) was found to decrease the availability of 5-phosphoribosyl-1-pyrophosphate (PRPP) and to decelerate the rate of de novo purine synthesis in suspensions of adult rat hepatocytes. Glucagon did not affect these parameters. The glucagon antagonist des-His1[Glu9]glucagon amide (DHGA), and the protein kinase C activator 1,2-dioctanoyl-sn-glycerol (DOG) were also found to lower PRPP availability. Incubation of the hepatocytes with dbcAMP or with DHGA, did not alter the activity of PRPP synthetase in the hepatocyte lysates, indicating that the above effects are not mediated through the activity of this enzyme. The possibility that the decrease in PRPP availability reflects increased consumption associated with accelerated pyrimidine synthesis is discussed. The decelerated rate of de novo purine synthesis is probably secondary to the decreased PRPP availability.

Animals↗
PubMed1997

Effects of reduced renal perfusion pressure and acute volume expansion on proximal tubule and whole kidney angiotensin II content in the rat.

In previous studies high luminal concentrations of angiotensin II (Ang II) were found in rat proximal tubules. The physiological role of intraluminal Ang II remains to be established. In the present study, we investigated whether the luminal angiotensin II concentration in the proximal tubules ([Ang II]prox) can be modulated. Micropuncture studies were performed in control rats (C, N = 8) and rats subjected to acute volume expansion (VE, N = 8) or reduced renal perfusion pressure (RRP, N = 7). Changes in [Ang II]prox were compared to changes in whole kidney Ang II content ([ANG II]kidney) and the plasma concentration ([Ang II] plasma). In C rats, [Ang II]prox was 460 +/- 48 pmol/liter (10 to 20 times lower than hitherto reported), while [Ang II]kidney and [Ang II]plasma were 369 +/- 81 pmol/kg and 90 +/- 29 pmol/liter, respectively. In agreement with previous data, VE failed to suppress [Ang II]prox (674 +/- 132 pmol/liter), while at the same time [Ang II]kidney (42 +/- 10 pmol/kg) and [Ang II]plasma (12 +/- 3 pmol/liter) were markedly suppressed. This points to dissociated regulation of [Ang II] in the renal luminal compartment on the one hand and the extraluminal renal and systemic plasma compartments on the other hand. During RRP, [Ang II]prox increased significantly to 1675 +/- 465 pmol/liter. No dissociation between the three compartments was observed in this situation, as [Ang II]kidney (969 +/- 85 pmol/kg) and [Ang II]plasma (245 +/- 72 pmol/liter) increased in parallel. In summary, we confirm that Ang II is present in proximal tubules of rat kidneys at concentrations which exceed those in plasma. Its concentration could be modulated (approximately 3.5 increase) by reduction of renal perfusion pressure but not by acute volume expansion. In the latter condition, we observed a clear dissociation from Ang II generation in the extraluminal renal compartment, as whole kidney Ang II content was markedly suppressed.

Angiotensin II↗
PubMed1997

Nifedipine attenuates systemic and renal vasoconstriction during nitric oxide inhibition in humans.

Clinical states associated with nitric oxide deficiency are often accompanied by vasoconstriction. We studied the effects of prolonged infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on systemic and renal hemodynamics in humans and the reversibility of the established vasoconstriction by calcium channel blockade with nifedipine. Seven healthy men underwent three 7-hour clearance studies. During one study, L-NMMA (3 mg/kg priming dose plus 3 mg.kg-1.h-1) was infused during hours 2 through 5, and during another study, nifedipine (0.015 mg/kg priming dose plus 0.015 mg.kg-1.h-1) was coinfused during hours 4 and 5. A third study served as time control. L-NMMA elicited reproducible systemic and renal vasoconstriction that was stable during the 4 hours of infusion. Systemic vascular resistance index, calculated from bioimpedance-derived cardiac index, increased from 22 +/- 1 to 29 +/- 2 mm Hg.min.m2.L-1 (P < .05). Mean arterial pressure rose by 4 +/- 1 mm Hg (P < .05), and heart rate, stroke index, and cardiac index decreased. Renal blood flow, calculated from renal plasma flow, decreased from 1182 +/- 101 to 785 +/- 53 mL/min, and renal vascular resistance increased from 73 +/- 5 to 115 +/- 6 mm Hg.min.L-1 (P < .05). Glomerular filtration rate decreased from 114 +/- 6 to 104 +/- 6 mL/min (P < .05), and filtration fraction increased. Sodium excretion fell from 89 +/- 9 to 32 +/- 7 mumol/min (P < .05). Nifedipine completely reversed systemic vasoconstriction. Nifedipine caused partial restoration of renal vascular resistance and complete normalization of glomerular filtration rate and sodium excretion but left the elevated filtration fraction unaltered. We conclude that sustained nitric oxide deficiency in humans is accompanied by strong systemic and renal vasoconstriction, decreased glomerular filtration rate, and sodium retention. Nifedipine can reverse most of these effects, suggesting a role for calcium channel blockade in pathological states of impaired nitric oxide activity.

Adult↗
PubMed1997

Nervous control of male sexual drive in the hermaphroditic snail

We studied the role of the prostate gland in determining the level of male sexual drive in the hermaphroditic pond snail Lymnaea stagnalis. Male sexual drive is high after a period of social isolation and decreases after copulation as a male. A positive correlation exists between the level of male sexual drive and the volume of the prostate gland. Like male sexual drive, the volume of the prostate gland increases during a period of social isolation and decreases after copulation as a male. Behavioural experiments demonstrated that animals with a lesion of the nerve that innervates the prostate gland (NP1) have a lower level of male sexual drive after social isolation than control animals. However, lesion of NP1 did not affect the increase in the volume of the prostate gland caused by social isolation. Extracellular recordings from NP1 in a semi-intact preparation show a change in firing pattern during an experimentally induced increase in prostate gland volume. The results indicate that NP1 serves as a nervous pathway for the male sexual drive. We propose a simple motivational model for male sexual behaviour in L. stagnalis in which the volume of the prostate gland sets the level of male sexual drive.

Journal Article↗