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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although angiotensin converting enzyme inhibitors and alpha 1-blockers have been reported to improve insulin sensitivity, their mechanisms of action have not been elucidated. To investigate the role of kinins in insulin sensitivity, we treated 4-week-old spontaneously hypertensive rats with either an angiotensin converting enzyme inhibitor (enalapril), an alpha 1-blocker (doxazosin), or an angiotensin II antagonist (losartan) for 3 weeks. A control group received no drugs. In addition, 18 rats treated with enalapril or doxazosin received a simultaneous administration of a kinin antagonist (Hoe 140). Glucose clamp testing was performed in each group. Enalapril (128 +/- 1 mmHg) and doxazosin (132 +/- 2 mmHg) decreased mean blood pressure compared with control levels (148 +/- 1 mmHg) (P < .01). The glucose requirement for the clamp test during the administration of enalapril (25.8 +/- 0.5 mg/kg per minute) or doxazosin (28.6 +/- 0.7 mg/kg per minute) was higher than that of the control group (19.8 +/- 0.5 mg/kg per minute) (P < .05). Although Hoe 140 did not alter the glucose requirement of doxazosin (27.8 +/- 0.5 mg/kg per minute), it decreased that of enalapril (22.6 +/- 0.9 mg/kg per minute) (P < .05) without affecting the changes in mean blood pressure induced by enalapril. In addition, losartan decreased mean blood pressure but did not affect the glucose requirement. Thus, the improvement in insulin sensitivity produced by an angiotensin converting enzyme inhibitor is mostly dependent on kinins but not on angiotensin II antagonism, and an alpha 1-blocker improves insulin sensitivity irrespective of kinins.
Hypertension 1994 Apr
PMID:Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor. 814 14

The contribution of endogenous kinins in the regulation of blood pressure of angiotensin-treated rats was evaluated using the new bradykinin B2-receptor antagonist Hoe 140 (D-Arg,[Hyp3,Thi5,D-Tic7, Oic8]-bradykinin). Chronic infusion of Hoe 140 at 75 nmol/d (a dose able to inhibit the vasodepressor effect of an intra-aortic bolus injection of 0.85 nmol/kg bradykinin) did not alter systolic blood pressure (tail-cuff plethysmography). Chronic infusion of angiotensin II (Ang II) induced a dose-related increase in systolic blood pressure and plasma Ang II levels. The vasopressor effect of 40 or 100 nmol/d Ang II was enhanced in rats given chronic infusion of Hoe 140 (by 12 and 14 mm Hg, respectively), whereas the increase in plasma Ang II levels remained unaltered. Furthermore, a low nonpressor dose of Ang II (20 nmol/d) was then able to increase blood pressure during chronic blockade of bradykinin receptors by Hoe 140 (from 126 +/- 3 to 137 +/- 3 mm Hg, P < .05). Combined infusion of 20 nmol Ang II and Hoe 140 did not alter the urinary excretion of sodium and water despite the fact that blood pressure was increased. Potentiation of the pressure effect of Ang II by Hoe 140 was confirmed by direct measurement of mean blood pressure (125 +/- 2 versus 108 +/- 2 mm Hg at 20 nmol, 123 +/- 2 versus 110 +/- 2 mm Hg at 40 nmol, and 139 +/- 2 versus 125 +/- 3 mm Hg at 100 nmol Ang II, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 May
PMID:Chronic inhibition of bradykinin B2-receptors enhances the slow vasopressor response to angiotensin II. 817 75

We investigated functional changes in aortic preparations of spontaneously hypertensive rats treated in utero and subsequently up to 20 weeks of age with the angiotensin converting enzyme (ACE) inhibitors ramipril (0.01 and 1 mg/kg per day) and perindopril (0.01 mg/kg per day). Early-onset treatment with the high dose of ramipril inhibited aortic ACE activity, prevented the development of hypertension, increased aortic vasodilator responses to acetylcholine (10(-8) to 10(-6) mol/L), decreased vasoconstrictor responses to norepinephrine (10(-8) mol/L), and increased aortic cyclic GMP content by 160%. Low-dose ramipril inhibited aortic ACE activity and attenuated the aortic vasoconstrictor response to norepinephrine but had no effect on blood pressure. Low-dose treatment with ramipril and perindopril resulted in a significant increase in aortic cyclic GMP content by 98% and 77%, respectively. Long-term coadministration of the bradykinin B2-receptor antagonist Hoe 140 abolished the ACE inhibitor-induced increase in aortic cyclic GMP. Our data demonstrate that long-term treatment with ACE inhibitors can alter vascular function of compliance vessels independently of the antihypertensive action. The increase in aortic cyclic GMP was due to bradykinin potentiating the action of the ACE inhibitors.
Hypertension 1993 Nov
PMID:Long-term low-dose angiotensin converting enzyme inhibitor treatment increases vascular cyclic guanosine 3',5'-monophosphate. 822 28

We studied the role of brain kinins in the regulation of cardiovascular function. Intracerebroventricular injection of 380 pmol bradykinin increased mean blood pressure by 20 +/- 2 mm Hg (P < .01) in normotensive Wistar-Kyoto (WKY) rats. Complete inhibition of this effect was achieved with intracerebroventricular administration of the newly synthesized, long-acting B2 receptor antagonist D-Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140). On a molar basis, Hoe 140 was two orders of magnitude more potent than antagonists of the first generation. Baroreceptor sensitivity, estimated as the heart rate response to blood pressure changes induced by intravenous injection of phenylephrine or sodium nitroprusside, was not altered by Hoe 140 in WKY rats. In spontaneously hypertensive rats (SHR), baroreceptor reflex sensitivity to increments in mean blood pressure was reduced by Hoe 140 (mean slope value: -0.47 +/- 0.07 versus -0.92 +/- 0.13 beats per minute per millimeter of mercury in controls, P < .05). Hoe 140 did not affect the tachycardic component of the baroreceptor reflex. Two-week intracerebroventricular infusion of Hoe 140 did not alter systolic blood pressure or heart rate in WKY rats. In SHR, systolic blood pressure increased (P < .01) similarly during the infusion of Hoe 140 or vehicle (from 174 +/- 6 to 220 +/- 5 mm Hg and 178 +/- 4 to 210 +/- 4 mm Hg at 2 weeks, respectively), whereas heart rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jan
PMID:Cardiovascular effects of brain kinin receptor blockade in spontaneously hypertensive rats. 828 56

We investigated the acute and chronic effects of converting enzyme inhibitors (captopril or enalapril) and of angiotensin II receptor blockade (DuP 753) on rapid (30-minute) baroreceptor resetting elicited by a prompt and sustained hypertensive response provoked by aortic constriction. Pressure-nerve activity curves, pressure at 50% of maximal baroreceptor activity, baroreceptor gain (slope of the curve), and systolic threshold pressure for baroreceptor activation were determined as indexes of baroreceptor function. A slight fall in mean arterial pressure after acute treatment with the converting enzyme inhibitor or DuP 753 was accompanied by a partial leftward curve shift, which is associated with a partial threshold shift and increase in gain. A maintained hypertensive stimulus caused a partial rightward curve shift and partial (49% to 56%) threshold shift to hypertensive levels in both acutely treated and control rats. The hypertensive stimulus provoked a partial rightward curve shift and complete (88% to 94%) threshold shift to hypertensive levels in chronically treated rats. The effect of enalapril on baroreceptor function was unaltered by the bradykinin antagonist Hoe 140. These data demonstrate that chronic inhibition of converting enzyme or blockade of angiotensin II receptors facilitates rapid resetting of the baroreceptors to hypertensive levels caused by partial aortic constriction without a change in baroreceptor sensitivity.
Hypertension 1994 Jan
PMID:Chronic converting enzyme inhibition facilitates baroreceptor resetting to hypertensive levels. 828 78

The contribution of endogenous kinins to the regulation of blood pressure, urinary volume, and renal sodium excretion was evaluated in Wistar rats on high sodium intake by using the new bradykinin receptor antagonist Hoe 140 (D-Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin). Neither Hoe 140 (3 nmol/hr s.c. for 4 weeks) nor its vehicle altered systolic blood pressure (tail-cuff plethysmography) or renal function in rats given saline solution (0.15 mol/L NaCl) to drink ad libitum. Four-week administration of deoxycorticosterone (DOC), combined with high sodium intake and uninephrectomy, increased systolic blood pressure from 127 +/- 3 to 160 +/- 3 mm Hg (p < 0.01). When long-term infusion of Hoe 140 was combined with DOC, high sodium intake, and uninephrectomy, systolic blood pressure rose from 127 +/- 3 to 175 +/- 3 mm Hg (p < 0.01). The hypertensive effect was greater in the Hoe 140 group (48 +/- 4 versus 33 +/- 3 mm Hg in controls, p < 0.05). This difference was confirmed by direct measurement of mean blood pressure (Hoe 140 group, 154 +/- 4 mm Hg; vehicle group, 139 +/- 4 mm Hg; p < 0.05). The antagonist blunted the increase in urinary volume induced by salt load and DOC in uninephrectomized rats, whereas it did not alter the increase in urinary sodium excretion. These results suggest that endogenous kinins do not play a major role in the regulation of normal blood pressure in sodium-loaded rats, whereas they may attenuate the hypertensive effect induced by long-term administration of mineralocorticoids and salt in uninephrectomized rats.
Hypertension 1993 Jun
PMID:Bradykinin B2-receptor blockade facilitates deoxycorticosterone-salt hypertension. 838 26

Spectral analysis was recently chosen to characterize the fast oscillations depending on the autonomic nervous system. Humoral stimuli could impinge on low frequency (LF) domain of blood pressure (BP) since the time lag to humoral systems activation is larger. This study was designed to analyse LF components of short-term variability of BP of conscious rats in conditions where humoral systems were activated. We studied rats with two-kidney Goldblatt hypertension in which the BP level was dependent upon the renin-angiotensin and kallikrein-kinin systems. Spectral powers of the systolic and diastolic BP and heart rate (HR) were computed in the high (respiratory, HF), mid (0.2-0.6 Hz, MF) and low (0.02-0.2 Hz, LF) frequency bands, as detected by the Fast Fourier Transform technique on consecutive 102-s stationary periods. Renal hypertension by a two-kidney one clip procedure was associated with a marked rise in SBP (+47 mmHg) and no significant change in HR. Renal hypertension selectively increased the LF component of SBP (+86%) when hypertensive rats were compared to sham operated animals. First, administration of losartan, a selective nonpeptide angiotensin II receptor antagonist, to sham rats resulted in a moderate SBP decrease, a significant tachycardia (+47 batt/min) with no change in BP and HR spectra profiles. Losartan determined in the hypertensive group a marked fall in SBP (-25 mmHg) with a significant tachycardia (+50 batt/min). Interestingly, losartan reduced the LF component of SBP (-26%). In a second series of normotensive and hypertensive rats, Hoe 140, a bradykinin B-2 receptor antagonist, did not affect the BP and HR levels of the two groups of rats. Hoe 140 decreased the LF component of SBP variability (-28%). Losartan, added after Hoe 140, decreased the BP (-17 mmHg) in association with a tachycardia (+59 batt/min) and induced a supplementary decrease of the LF component of SBP variability (-60%) in hypertensive rats. After the combined blockade, the LF component of SBP of the hypertensive rats was equivalent to that of the sham rats. Thus, an increase in the LF component of BP variability was observed in a model of hypertension where the BP is dependent upon humoral factors. The contribution of the renin-angiotensin and kallikrein-kinin systems in the slow fluctuations of BP was demonstrated using two specific antagonists losartan and Hoe 140.
 ...
PMID:[Hormonal contribution to short-term variability of blood pressure in a renovascular hypertension model]. 857 74

1. The long-term reduction in blood pressure following ACE inhibitor treatment in young spontaneously hypertensive rats (SHR) appears to depend on both the kidney and bradykinin. 2. The aim of this experiment was to examine the effects of ACE inhibition and bradykinin on renal morphology and blood pressure in SHR. 3. Between 6 and 10 weeks of age male SHR received one of four treatments: water (n = 26), ramipril (1 mg/kg per day; n = 24), ramipril (1 mg/kg per day) plus Hoe 140 (0.5 mg/kg per day; n = 25) or Hoe 140 (0.5 mg/kg per day; n = 25). 4. Renal medullary and cortical volumes were determined stereologically at 10 and 20 weeks of age. 5. After 4 weeks of treatment, ramipril reduced the size of the renal medulla while Hoe 140 increased medullary volumes compared to control. Ten weeks after treatment was stopped the renal medulla of the ramipril group had returned to normal, however, there was a persistent increase in medullary volume of both Hoe 140 treated groups. 6. Our results imply that bradykinin may influence the size of the renal medulla which may have important effects on the development of hypertension in SHR.
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PMID:Renal medulla and bradykinin during the development of hypertension in SHR. 858 4

After transient episodes of ischemia, benefits of thrombolytic or angioplastic therapy may be limited by reperfusion injury. Angiotensin-converting enzyme inhibitors protect the heart against ischemia/reperfusion injury, an effect mediated by kinins. We examined whether the protective effect of the angiotensin-converting enzyme inhibitor ramiprilat on myocardial ischemia/reperfusion is due to kinin stimulation of prostaglandin and/or nitric oxide release. The left anterior descending coronary artery of Lewis inbred rats was occluded for 30 minutes, followed by 120 minutes of reperfusion. Immediately before reperfusion rats were treated with vehicle, ramiprilat, or the angiotensin II type 1 receptor antagonist losartan. We tested whether pretreatment with the kinin receptor antagonist Hoe 140, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor indomethacin blocked the effect of ramiprilat on infarct size and reperfusion arrhythmias. In controls, infarct size as a percentage of the area at risk was 79 +/- 3%; ramiprilat reduced this to 49 +/- 4% (P < .001), but losartan had little effect (74 +/- 6%, P = NS). Pretreatment with Hoe 140, NG-nitro-L-arginine methyl ester, or indomethacin abolished the beneficial effect of ramiprilat. Compared with the 30-minute ischemia/120-minute reperfusion group, nonreperfused hearts with 30 minutes of ischemia had significantly smaller infarct size as a percentage of the area at risk, whereas in the 150-minute ischemia group it was significantly larger. This suggests that reperfusion caused a significant part of the myocardial injury, but it also suggests that compared with prolonged ischemia, reperfusion salvaged some of the myocardium. Ventricular arrhythmias mirrored the changes in infarct size. Thus, angiotensin-converting enzyme inhibitors protect the myocardium against ischemia/reperfusion injury and arrhythmias; these beneficial effects are mediated primarily by a kinin-prostaglandin-nitric oxide pathway, not inhibition of angiotensin II formation.
Hypertension 1996 Jan
PMID:Paracrine systems in the cardioprotective effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury in rats. 859 91

The contribution of endogenous kinins to impairment in renal adaptation to a 6-day period of dietary sodium withdrawal associated with treatment with ramipril (5 mg/kg per day) and losartan (30 mg/kg per day) was evaluated by use of concomitant chronic administration of the bradykinin B2-receptor antagonist Hoe 140 (150 or 300 micrograms/kg per day via subcutaneous osmotic pump). A similar level of higher cumulative sodium excretion was observed in ramipril- and losartan-treated rats compared with untreated animals, and the effect of ramipril was not affected by Hoe 140. Similarly, the fall in arterial pressure and the renal vasodilatation associated with ramipril and losartan were not modified by Hoe 140. Glomerular filtration rate (785 +/- 73 microL/min per g KW in untreated sodium-depleted rats) decreased to a larger extent in ramipril-treated rats compared with losartan-treated rats (371 +/- 78 and 550 +/- 55 microL/min per g KW, respectively). Hoe 140 markedly prevented the alteration in glomerular filtration rate associated with ramipril, thus resulting in a final glomerular filtration rate (543 +/- 41 microL/min per g KW) similar to that observed with losartan. These findings demonstrate that despite a lack of influence on arterial pressure and sodium balance, accumulation of kinins markedly contributes to deterioration of the glomerular filtration rate induced by ramipril in sodium-depleted rats.
Hypertension 1996 Jan
PMID:Chronic kinin blockade and effect of ramipril in renal adaptation to sodium restriction. 859 93


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