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Biomedical subjects

F M Lai

Publications and source records attributed to F M Lai.

At least 145 records · Page 8Linked to original sources
PubMed1983

Hypotensive and vasodilatory activity of (+/-) 1-o-octadecyl-2-acetyl glyceryl-3-phosphorylcholine in the normotensive rat.

Synthetic (+/-) 1-O-octadecyl-2-acetyl-glyceryl-3-phosphorylcholine (octadecyl-AGPC) in microgram/kg doses given intravenously effectively and potently lowered mean arterial blood pressure in conscious and anesthetized normotensive rats. The hypotensive activity was much more pronounced in the anesthetized rat than in the conscious rat. The hypotension was associated with a significant elevation in plasma renin activity (PRA). In the rat in which the hindquarters were perfused, octadecyl-AGPC given intraarterially effectively decreased the perfusion and systemic pressures in a dose-dependent manner. Pharmacological blockade with specific cholinergic, histaminergic or beta-adrenergic receptor antagonists, did not block or attenuate the octadecyl-AGPC-induced reduction in perfusion or systemic pressure. These results suggest that the hypotensive activity of octadecyl-AGPC in the normotensive rat is the result of direct vasodilation and not the result of cholinergic, histaminergic or beta-adrenergic receptor interaction.

Acetylcholine↗
PubMed1983

Antihypertensive agents: angiotensin converting enzyme inhibitors. 1-[3-(Acylthio)-3-aroylpropionyl]-L-prolines.

A series of 1-[3-(acylthio)-3-aroylpropionyl]-L-proline derivatives was synthesized. A number of these compounds are potent angiotensin converting enzyme (ACE) inhibitors that lowered blood pressure in aorta-coarcted renal hypertensive rats. The most active derivatives are 1-[3(R)-(acetylthio) -3-substituted-benzoyl)-2(S)-methyl-propionyl]-L-prolines with an in vivo activity equivalent to SQ 14,225 (captopril). Structure-activity relationships are discussed. Changes in the configuration of the alpha-methyl group and the S-acetyl group affect the ACE activity. Coupling of 3-(substituted-benzoyl)-2-methylpropionic acids to L-proline via enol lactones is described.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Aortic vascular and atrial responses to (+/-)-1-O-octadecyl-2-acetyl-glyceryl-3-phosphorylcholine.

The effects of (+/-)-1-O-octadecyl-2-acetyl-glyceryl-3-phosphorylcholine (octadecyl-AGPC) were studied in three types of aortic vascular smooth muscle preparations, namely, strips, rubbed and unrubbed rings, and an atrial preparation in normotensive rats. In the resting tension state, octadecyl-AGPC did not elicit significant contractions in either rubbed or unrubbed ring preparations at concentrations lower than 1 X 10(-4) M. However, at a concentration of 3 X 10(-4) M, octadecyl-AGPC markedly contracted both types of ring preparations. This contractile response was partially antagonized by pretreatment with reserpine and completely blocked by phentolamine (1 X 10(-6) M). In preparations contracted with noradrenaline (NA), octadecyl-AGPC elicited biphasic responses in intact ring preparations; an initial relaxation followed by contraction. Octadecyl-AGPC induced only a slight contraction in strips and a slight relaxation in the rubbed ring preparation. Octadecyl-AGPC did not elicit any significant effect on chronotropy or inotropy at concentrations up to 3 X 10(-5) M. When the concentration was 1 X 10(-4) M, octadecyl-AGPC produced significant positive chronotropic and inotropic effects on spontaneously beating right and electrically driven left atrial preparations, respectively. Both effects were blocked by propranolol (5 X 10(-8) M); reserpine pretreatment antagonized only the chronotropic response. In [3H]-dihydroalprenolol [( 3H]-DHA) binding studies, octadecyl-AGPC had a Kd of 427.85 microM and thus was much less potent than isoprenaline (Kd = 465.10 nM) or propranolol (Kd = 4.4 nM) in displacing [3H]-DHA in rat cardiac membrane preparations. 6 In conclusion, relaxation and contraction induced by octadecyl-AGPC in aortic preparations is an indirect rather than a direct effect. An unknown factor released from endothelial cells is responsible for aortic smooth muscle relaxation by octadecyl-AGPC while released NA appears to be responsible for aortic vascular contraction and for the positive chronotropic and inotropic effects in the atrial preparations.

Animals↗
PubMed1983

Effect of caloric restriction on cardiac reactivity and beta-adrenoceptor concentration.

The effect of a 21-day program of caloric restriction on cardiac reactivity and beta-adrenoceptor number was investigated in male Sprague-Dawley rats. Rats on the restricted diet (Restricted) exhibited significant decreases in body weight, epididymal fat pad, and retroperitoneal fat pad weight as well as the percent of body fat represented by these adipose tissue depots when compared with rats fed ad libitum (Fed). Fed rats exhibited significantly increased total heart weight and total heart protein, but the percent cardiac protein and ratio of heart weight to body weight were similar in Fed and Restricted rats. Isolated atria from Fed and Restricted rats developed similar chronotropic and inotropic responses over a range of isoproterenol concentrations. Although total beta-adrenoceptor number (fmol/heart) was greater in Fed rats, the concentration of beta-adrenoceptors (fmol/mg protein) was remarkably similar regardless of the dietary regimen. Therefore, despite significant decreases in body weight, body fat, and heart weight, the myocardium of Restricted rats maintained the capability of responding to isoproterenol as that of Fed rats, the mechanism of which is at least partially mediated through maintenance of beta-adrenoceptor concentration.

Animals↗
PubMed1983

CL 115,347 (DHV-PGE2 ME): a new orally and topically active prostaglandin antihypertensive agent.

CL 115,347 orally (0.25-10 mg/kg) and topically (0.03 and 0.1 mg/kg) lowered blood pressure in a dose-dependent manner in conscious spontaneously hypertensive rats (SHR). Duration of action of the oral dose range was from 1 to more than 8 h and of the topical dose range, from more than 6 to more than 24 h. CL 115,347 was 100-200 times more potent orally and greater than 250 times more potent topically than l-prostaglandin (PG) E2. When 3 mg/kg was administered orally, CL 115,347 was also active in Dahl "S" salt-sensitive hypertensive rats, deoxycorticosterone acetate-salt hypertensive rats, aorta-coarcted renin-dependent hypertensive rats, normotensive rats, bilaterally nephrectomized SHR, and bilaterally ureteral-ligated SHR. CL 115,347 was also orally active at 0.1 mg/kg in normotensive rhesus monkeys and in renal hypertensive dogs at 1 mg/kg. CL 115,347 was as active as l-PGE2 in relaxing the rabbit ear arterial smooth muscle in vitro. In anesthetized dogs, CL 115,347 injected intra-arterially (0.5-10 micrograms) into the vascular bed being studied increased blood flow to femoral, carotid, coronary, superior mesenteric, and renal vascular beds. CL 115,347 decreased vasopressor responses induced by electrical stimulation of the spinal cord at T7-T9 but did not decrease the tachycardia induced by stimulation of the cardioaccelerator segments (C7-T1) in pithed SHR. CL 115,347 has a broad spectrum of antihypertensive activity in various animal models and probably exerts its major antihypertensive effects through relaxation of blood vessels.

Administration, Oral↗
PubMed1982

Disposition of catecholamines in cardiovascular tissues of aorta coarcted hypertensive rats.

Aorta-coarcted hypertensive rats and sham-operated normotensive rats were compared in order to assess the contribution of sympathetic nervous system activity to the elevated blood pressure in these rats at an early (6 days) and chronic (42 days) stage of hypertension. Norepinephrine (NE), epinephrine (E) and dopamine (DA) levels were quantitated in plasma, heart and vascular tissues (aorta, inferior vena cava, mesenteric artery and vein) using a radioenzymatic procedure. Body weight was significantly reduced and mean arterial blood pressure (MABP) significantly increased in the coarcted rats at both stages of hypertension. Plasma catecholamines did not differ at either stage of hypertension. The NE content of the heart and mesenteric artery was significantly decreased in the coarcted rats at both stages of hypertension but unchanged in the other vessels studied. E and DA levels in the heart and all vasculature analyzed remained unaltered at both stages of hypertension. The present results suggest that neither E nor DA makes a major contribution to the development and maintenance of hypertension in the aorta-coarcted rat. The observation of the reduced cardiac NE concentration in the coarcted rats together with literature reports of similar observations in other animal models of hypertension suggests that myocardial NE depletion is a common feature of the hypertension and not dependent on the methodology used to produce that hypertension.

Animals↗
PubMed1982

Studies on the mechanism of the enhancement of the antihypertensive activity of captopril by a diuretic in spontaneously hypertensive rats.

Captopril (30 mg/kg/day orally for two days) in spontaneously hypertensive rats (SHR) inhibited serum angiotensin converting enzyme (ACE) activity 92.3%; increased plasma renin activity (PRA) 18-fold and reduced mean arterial blood pressure (MABP) 19 mm Hg. Hydrochlorothiazide (HCTZ) (100 mg/kg-day 1; 10 mg/kg-day 2, orally) increased PRA 3-fold but did not affect serum ACE or MABP. HCTZ plus captopril inhibited serum ACE 95.2%; increased PRA 38-fold and reduced MABP 47.5 mm Hg. Captopril or HCTZ plus captopril did not alter the responses of isolated aortic strips to norepinephrine (NE), serotonin, angiotensin II (AII) or isoproterenol. Pressor responses of conscious SHR to AII and NE were unaltered by captopril or HCTZ plus captopril although the bradykinin-induced depressor responses were significantly but equally potentiated. These results suggest that the potentiating effect of HCTZ is due to some mechanism that shifts the animal's blood pressure maintenance system to a renin-dependent state and is not due to changes in vascular reactivity.

Angiotensin II↗
PubMed1981

A comparison of cardiac reactivity and beta-adrenoceptor number and affinity between aorta-coarcted hypertensive and normotensive rats.

1 The effects of noradrenaline (NA) and isoprenaline on isolated atria from aorta-coarcted hypertensive rats (AHR) at early (6 day) and chronic (28 day) stages of hypertension were studied and compared with time-matched, sham-operated, normotensive rats (SNR). The number and affinity of beta-adrenoceptor ((-)-[3H]-dihydroalprenolol binding sites) were also studied in cardiac membranes prepared from these animals. 2 Six and 28 days after complete ligation of the abdominal aorta between the two renal arteries, rats became hypertensive with significantly greater arterial blood pressures than time-matched SNR. 3 At both stages of hypertension, the atrial inotropic or chronotropic effects of NA and isoprenaline from hypertensive rats were similar to time-matched SNR. Moreover, no differences in atrial reactivity were observed between the early and chronic stages of hypertension. 4 Irrespective of the stage of hypertension, cardiac membranes from the AHR contained the same number of beta-adrenoceptors as time-matched SNR. In addition, the receptor affinity for the radioligand within each group was equivalent. However, the chronic stage hypertensive rats and their time-matched controls contained fewer beta-adrenoceptors and these receptors had greater affinity for the radioligand when compared with cardiac membranes from rats at the early stage of hypertension and their controls. 5 The observed equivalent chronotropic and inotropic responses to NA and isoprenaline between the hypertensive and normotensive rats in both stages of hypertension may be explained in terms of similar receptor number and receptor binding affinity. 6 The reduced number of beta-adrenoceptors with greater binding affinity in day 28 normotensive or hypertensive rats may be a compensatory mechanism for these animals to maintain normal cardiac function with increasing age.

Animals↗
PubMed1980

Effect of the time interval between blood sampling and assay on serum angiotensin I-converting enzyme activity from captopril-treated rats.

Intra-arterial injection of captopril (1 mg/kg) effectively lowered arterial blood pressure in aorta-coarcted hypertensive rats along with an associated reduction of serum angiotensin I-converting enzyme (ACE) activity. ACE activity in serum samples from captopril-treated animals that were assayed within 60 min after collection was inhibited 93%. However, this inhibition progressively decreased as the interval between time of assay and blood collection increased. This information would appear to be of considerable value in planning experiments for the determination of serum ACE activity from captopril-treated animals.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1980

Effects of different stages of aortic coarctation hypertension on aortic contraction and relaxation in rats.

Contractile responses to norepinephrine, serotonin and potassium (K+) and relaxant responses to isoproterenol and papaverine were studied in vitro with spirally cut thoracic aortic strips from aortic coarcted hypertensive rats (AHR)2, 6, 14 and 28 days postoperatively and compared to time-matched, sham-operated normotensive controls. At every stage after coarctation, the rats developed hypertension with elevated plasma renin activity. In response to stimulation by norepinephrine and serotonin, aortic strips from 2 to 28 day AHR developed the same tension as controls, whereas aortas of 6 and 14 day AHR had reduced maximal responses. For K+-stimulated aortic strips, maximal contractile force was decreased at 6 day AHR only. Relaxation by isoproterenol and papaverine in serotonin-contracted aortas was the same in AHR and normotensive controls 2 and 28 days postoperatively but was reduced at 6 and 14 days. The demonstrated changes of vascular contractility and relaxation in AHR is a hypertensive stage-dependent phenomenon. It is speculated that 6 and 14 days after coarctation the diminished relaxant ability of the aortas helps to maintain the elevated blood pressure and the diminished sensitivity to contractile stimulants is a protective mechanism in response to the elevated blood pressure. The return of normal contraction and relaxation to the agonists in the chronic stage of hypertension may possibly reflect an adaptive change to the prolonged stimulus of the elevated blood pressure that aortic tissue had undergone in order to maintain normal physiologic functions.

Animals↗
PubMed1978

Monoamine oxidase activity in tissues of spontaneously hypertensive rats.

Monoamine oxidase (MAO) activity was assayed both in central and peripheral blood vessels of spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKR). The activity of MAO in the brain and peripheral vasculature was essentially the same in both SHR and WKR. It can therefore be concluded that central and peripheral vascular MAO activity is not altered in the genetically hypertensive animals.

Animals↗
PubMed1978

Studies on the monoamine oxidase and catechol-O-methyltransferase of the rat cerebral microvessels.

The rat cerebral microvessels were isolated and assayed both for monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT) activities. Cerebral microvessels and brain filtrate were found to contain both forms (A & B) of MAO. On a per mg protein basis, the cerebral microvessels contained the greatest activity of MAO and COMT than that of brain filtrate and mesenteric artery. Chemical sympathectomy using 6-hydroxydopamine neither decreased total MAO activity, nor the A form of the enzyme, nor did it have any effect on COMT activity in the brain microvessels. These results suggest that COMT and both forms of MAO in the rat brain microvessels are extraneuronal in origin.

Animals↗
PubMed1978

The potentiating effect of clorgyline and pyrogallol on the blood pressure responses to norepinephrine.

Intraventricular administration of norepinephrine (NE) into pentobarbital anesthetized rats elicits a pressor or a depressor effect depending on the dose injected: after a low dose, a depressor response is seen while after a high dose, a pressor response is observed. In the animal pretreated intraventricularly with clorgyline or pyrogallol, the hypotensive effect of a low dose of NE was reversed to a hypertensive effect, while the hypertensive effect of a high dose of NE was markedly potentiated. This result suggests that brain monoamine oxidase and catechol-o-methyltransferase can metabolize centrally released NE before it leaks into the peripheral circulation.

Animals↗
PubMed1977

Brain and vascular monoamine oxidase activity in the deoxycorticosterone-salt hypertensive rat.

1 The role of monoamine oxidase (MAO) in the maintenance of deoxycorticosterone-sodium chloride (DOCA-salt) hypertension was investigated by assaying the MAO activity both in central as well as peripheral blood vessels and in brain tissue. 2 The results suggest that the activity of MAO in the DOCA-salt hypertensive rat is similar to the activity present in the normotensive rat.

Animals↗