Lyon Hypertensive Rats Research Articles

Cardiovascular habituation to emotional stress in Lyon hypertensive rats.

1. Intra-aortic blood pressure was recorded continuously in freely moving genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) rats of the Lyon strain during two 11 h periods (08:00-19:00 h). During the first period (control), the animals were left undisturbed and during the second period (stress), a jet of air was applied for 20 min every hour. Urine was collected simultaneously and analysed for its content in norepinephrine and epinephrine. 2. The first exposure to the stressor induced larger increases in blood pressure and heart rate in LH than in LN and LL rats. However blood pressure and heart rate responses to the 10 following stressors decreased in LH rats while they remained stable in LN and LL animals. 3. Repeated stress exposure induced significant increases in epinephrine excretion in both LN and LL but not in LH rats. 4. It is concluded that LH rats exhibit marked cardiovascular habituation to repeated stress. Taken together with the lack of stress-induced sympathoadrenal activation, this suggests a reduced level of emotional responsiveness in Lyon hypertensive rats.

Blood pressure maintenance in hypertensive sympathectomized rats. I. Adrenal medullary catecholamines

To assess the role of the sympathetic nervous system in the development of genetic hypertension, blood pressure (BP) was recorded in conscious adult Lyon hypertensive (LH) and normotensive (LN) rats that had received daily injections of saline or guanethidine at 1-13 wk of age. Guanethidine abolished the pressor response to tyramine, decreased plasma norepinephrine by greater than 70% and plasma 3,4-dihydroxyphenylglycol by approximately 90%, and did not change plasma epinephrine. Bilateral adrenalectomy further reduced plasma norepinephrine to 8 and 5% of control levels in LH and LN rats, respectively. BP was lowered (-7%) in sympathectomized rats, but the mean absolute BP difference between LH and LN rats was unaltered. Despite marked supersensitivity to alpha-adrenoreceptor stimulation, phentolamine induced only a small transient depressor response, which was abolished by adrenalectomy in sympathectomized rats. It is concluded that the sympathetic nervous system is not necessary for the development of hypertension in LH rats. After sympathectomy, circulating catecholamines, which mostly derive from the adrenal medulla, play only a minor role in BP maintenance.

Renal denervation does not prevent hypertension in Lyon hypertensive rats

The effects on blood pressure (BP) of a single and repeated renal denervations (RD) were compared in genetically hypertensive (LH) and normotensive (LN) rats of the Lyon strain. Indirect BP was measured by the tail-cuff method, and direct BP was measured through an aortic catheter in conscious quiet rats receiving a normal-sodium diet. Single RD (10 wk of age) did not reduce BP in both LN and LH rats. Repeated RD (4, 7, and 10 wk of age) partly prevented the age-related increase in tail-cuff BP but did not affect the directly recorded BP in 11-wk-old LH rats. Single and repeated RD reduced the renal norepinephrine content by greater than 90%. Both procedures did not alter the BP lowering effects of angiotensin-converting enzyme inhibition and of ganglionic blockade. It is concluded that renal nerves are not necessary for the development and the maintenance of hypertension in LH rats.

Adrenergic stimulation of renal prostanoids in the Lyon hypertensive rat.

Young, genetically hypertensive Lyon (LH) rats exhibited an increased renal in vivo turnover of norepinephrine and an elevated urinary excretion of thromboxane B2 when compared with normotensive (LN) and low blood pressure (LL) controls. Therefore, the effects of norepinephrine (1.2 x 10(-8) to 9.6 x 10(-7) M) and of phenylephrine (5 x 10(-8) to 1.9 x 10(-6) M) on renal function and the urinary excretion of prostanoids were assessed in isolated perfused kidneys of 8-week-old LH, LN, and LL rats. In addition, the effects of norepinephrine were assessed before and during thromboxane A2/prostaglandin H2 receptor blockade by AH23848 (4 x 10(-6) M). Before drug infusion, LH kidneys differed from those of LN and LL controls by having an elevated renal vascular resistance and a decreased natriuresis and glomerular filtration rate; the urinary output of prostaglandin E2 and F2 alpha, of 6-ketoprostaglandin F1 alpha, and of thromboxane B2 was similar in the three strains. The constrictor effects of norepinephrine and phenylephrine were significantly increased in LH rat kidneys compared with LL but not with LN controls, and their pressure-natriuresis was markedly reduced. Norepinephrine and phenylephrine induced a 10- to 20-fold dose-dependent increase in the synthesis of the four prostanoids, which was more pronounced in LH than in LN and LL rats for thromboxane B2 only. AH23848 infusion significantly reduced the vascular effects of norepinephrine and increased the natriuretic response of LH but not of LN and LL rat kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Thromboxane A2 and development of genetic hypertension in the Lyon rat strain.

To determine whether the increased renal biosynthesis of thromboxane A2 observed in young genetically hypertensive rats of the Lyon strain could be involved in the development of their hypertension, Lyon hypertensive female rats received either thromboxane synthetase inhibitors (Dazmegrel or OKY 046) or a thromboxane A2 receptor antagonist (AH 23848) during their prehypertensive stage. Treatment from 5 to 9 weeks of age with Dazmegrel failed to reduce systolic blood pressure. When given from 3 to 9 weeks of age, Dazmegrel and OKY 046 induced a similar progressive and specific reduction (60%) in the urinary excretion of thromboxane B2 that was associated with a transient decrease in blood pressure level with Dazmegrel and a longer lasting blood pressure-lowering effect with OKY 046. AH 23848, given according to the same schedule, normalized the blood pressure level. This effect persisted 1 week after the cessation of the treatment. Interestingly, active doses of thromboxane synthetase inhibitors or of thromboxane A2 receptor blocker required a 3-week delay to exhibit their antihypertensive properties. It is concluded that 1) the elevated production of thromboxane A2 observed in young Lyon hypertensive rats is likely to participate actively in their blood pressure regulation and 2) this effect may be independent of its direct vasoconstrictor properties.

Parathyroidectomy in the Lyon hypertensive rat: cardiovascular reactivity and aortic responsiveness

We have studied the effect of parathyroidectomy on the systolic blood pressure, cardiovascular reactivity and the contractile response of isolated aorta to norepinephrine in the genetically hypertensive Lyon rat strain (LH), parathyroidectomized hypertensive Lyon rats (LH-PTX) and parathyroidectomized hypertensive Lyon rats given a Ca-enriched diet to re-establish normocalcemia (LH-PTX + Ca). Parathyroidectomy significantly lessened (-20%) the development of elevated blood pressure. In the LH-PTX + Ca, the blood pressure was lower than that of LH controls but was higher than that of LH-PTX. At 23 weeks, in vivo responsiveness to norepinephrine and angiotensin II was significantly lower in the LH-PTX and only slightly decreased in the LH-PTX + Ca. In contrast, at the same age, the in vitro contractile response of isolated aortas to norepinephrine was significantly higher in the LH-PTX compared with other groups. Interestingly, without endothelium, this difference disappeared. In conclusion, parathyroidectomy lessened the blood pressure elevation in the Lyon model of hypertensive rats via mechanisms that are partly independent of serum calcium levels.

Dietary Calcium, Vascular Reactivity, and Genetic Hypertension in the Lyon Rat Strain

In order to examine the relationship existing between dietary calcium and the development of hypertension, we developed a long-term study in the Lyon hypertensive rat strain (LH) and two control strains, the Lyon normotensive (LN) and low blood pressure rats (LL) given enriched (HCa, 2.5%), deprived (LCa, 0.03%) and normal (NCa, 0.6%) calcium diets. Evolution of body weight, systolic blood pressure (BP), plasma calcium and magnesium was monitored from 4 to 23 weeks of age. Total cardiovascular reactivity and contractile response of isolated aorta to norepinephrine were measured at 23 weeks of age. LH rats on HCa diet failed to develop hypertension (BP less than 150 mm Hg) whereas LH rats on LCa diet exhibited higher blood pressure levels than their controls fed the NCa diet. Moreover, in LN rats HCa diet slightly decreased BP whereas LCa had no effect. In the LL rats, on the contrary, only LCa diet slightly increased BP. In vivo responsiveness to NE was significantly higher in LH compared to LL and LN rats fed a NCa diet. HCa and LCa diets both induced a significant decrease in this response in LH rats. HCa diet increased the response in LN rats but decreased it in LL. In contrast, at the same age, the in vitro contractile response of isolated aorta to NE was significantly decreased in LH compared to LN and LL rats receiving NCa diet. Moreover in LH and LN rats on HCa diet the contractile response was markedly increased but no significant difference was observed with LCa diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of the renin gene intron A tandem repeat region of Milan and Lyon hypertensive rat strains

The region of intron A of the rat renin gene containing a unique tandemly repeated sequence was analysed in the Milan and Lyon hypertensive rat strains and their controls, and in several Sprague-Dawley rats, using an oligonucleotide probe complementary to the tandemly repeated sequence and a renin complementary DNA probe. In the Milan rats, the size of the Bgl II DNA fragment encompassing the tandem repeat region was the same in the hypertensive (MHS) and normotensive (MNS) strains. In the Lyon model, a difference of 1.1 kilobase (equivalent to about 28 copies of the 38 basepair tandem repeat sequence) was observed in the size of the Bgl II fragment of the hypertensive (LH) and normotensive (LN) strains. However, the finding that the size of the fragment in the Lyon low-blood-pressure (LL) strain was the same as that in the LH strain rather than the LN strain suggests that the difference between the two latter strains is not by itself a major cause of the blood pressure difference between them in the intron A tandem region. An analysis of Sprague-Dawley rats, from which the Lyon strains are derived, showed that at least three different renin gene alleles, two with Bgl II fragments of the same size as those seen in the Lyon strains, are randomly segregating in this population.

Noradrenaline content and adrenergic receptors in kidney and heart of the prehypertensive and hypertensive Lyon rat strain.

Sympathetic activity modulates the blood pressure in part by activation of cardiac and renal adrenergic receptors. Thus an alteration of tissue noradrenaline content and/or adrenergic receptors in heart and kidney might be involved in the pathogenesis of hypertension. In order to verify this possibility, we studied tissue noradrenaline content and alpha and beta adrenergic receptors in the heart and kidney of Lyon hypertensive (LH), normotensive (LN), and low-pressure (LL) rats. Density and affinity of receptors were determined using the specific radioligands [3H]-prazosin (alpha 1), [3H]-rauwolscine (alpha 2), and [3H]-dihydroalprenolol (beta) in prehypertensive (5-week-old) and hypertensive (21-week-old) rats. In the prehypertensive period, no differences concerning renal and cardiac noradrenaline content and adrenergic receptor densities and affinities were observed. In the hypertensive period, an age-related decrease of renal alpha 1 and beta receptors was observed in LN and LL (P less than 0.01) but not in LH rats. Consequently, at this time, density of renal alpha 1 and beta receptors was higher in LH than in LN and LL (P less than 0.01). In contrast, the density and affinity of renal alpha 2 and cardiac alpha 1 and beta receptors and tissue noradrenaline content were similar in the three rat strains. Because renal alpha 1 and beta receptors mediate various functions involved in the control of blood pressure such as tubular sodium reabsorption, renin secretion, and glomerular filtration, the different density of these receptors in LH rats might be involved in the development or maintenance of hypertension.

Cardiovascular reactivity of genetically hypertensive rats of the Lyon strain

The cardiovascular sensitivity to noradrenaline (NA), phenylephrine (PE) and angiotensin II (A II) was determined in male rats of the Lyon hypertensive (LH) and normotensive (LN) strains. This study was conducted in young (eight week-old) prehypertensive and in older (21 week-old) LH rats with established hypertension. cardiovascular sensitivity was assessed in the pretreated anesthetized rat by measuring the height (Δ MAP) and the surface of the mean arterial pressure (MAP) peaks evoked by the i.v. injection of different doses of vasoconstrictors. In eight week-old LH rats compared to LN controls the Δ MAP for NA, PE and A II were normal while MAP peak surfaces for NA and A II but not for PE were significantly increased. Twenty-one weekold LH rats exhibited greater Δ MAP and MAP peak surfaces for the three agonists used than did the LH controls. Cocaine injection increased more markedly the responses to NA of 21 week-old LH rats than of LN rats which suggests an enhanced neuronal uptake of NA in adult LH animals.

Plasma lipids in genetically hypertensive rats of the Lyon strain.

Of the four standardized strains of genetically hypertensive rats, only the Lyon hypertensive rats spontaneously exhibit a higher body weight than their normotensive controls. In order to determine if this increased body weight is associated with alterations in the lipid metabolism, plasma triglycerides (TG), phospholipids (PL), total cholesterol (TPC), and high-density lipoprotein cholesterol (CHDL) were followed in Lyon hypertensive (LH), normotensive (LN), and hypotensive (LL) male rats between 5 and 32 weeks of age. TG were stable with age in LL and LN but increased in LH rats. PL decreased in LL, remained stable in LN, but increased with age in LH rats. TPC and CHDL were stable in LL and LN and increased with age in LH rats. Plasma lipids were not related to the blood pressure level, but were positively related to the body weight in the hypertensive strain. Thus, starting at the age of 5 weeks, LH rats exhibit spontaneously a significant increase in blood pressure, body weight, and plasma lipid concentrations.