Spontaneously hypertensive rat SHR

The antioxidant property of ferulic acid and related compounds from rice bran was reported by Kikuzaki et al, (2002). Their results indicated that these compounds elicit their antioxidant function through radical scavenging activity and their affinity with lipid substrates. Another recent study reported by Butterfield et al, (2002) demonstrated that ferulic acid offers antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro. The effect of ferulic acid on blood pressure (BP) was investigated in spontaneously hypertensive rats (SHR). After oral administration of ferulic acid the systolic blood pressure (SBP) decreased in a dose-dependent manner. There was a significant correlation between plasma ferulic acid and changes in the SBP of the tail artery, suggesting... 

N5. Newaz, M. A., and Nawal, N. N., Effect of gamma-tocotrienol on blood pressure, lipid peroxidation and total antioxidant status in spontaneously hypertensive rats (SHR). Clin. Exp. Flypertens. 

In the spontaneously hypertensive rat (SHR) SK F 82526 was inactive as a natriuretic, but was active as an antihypertensive agent. The weaker natriuretic activity of SK F 82526 compared to SK F 38393 was also seen in conscious dog renal clearance studies (27). SK F 82526 given 5 mg/kg p.o. increased renal plasma flow 81%, glomerular filtration rate 15%, but elevated sodium excretion only about half the amount observed with SK F 38393, and this in a somewhat delayed response. SK F 82526 when given in the drinking water at 200 mg/kg/day for 30 days in developing SHR blunted the onset of hypertension and also lowered blood pressure acutely in anesthetized SHR. It did not lower blood pressure in anesthetized Dahl salt sensitive hypertensive rats. 

Thieno[3,4-d]pyrimidine-2(l//),4-dione 312 exhibited potent oral antihypertensive activity in spontaneously hypertensive rats (SHR) with a 0.21 mg/kg dose required for reducing systolic blood pressure (SBP) by 50 mm Hg (ED50sbp)- The ED50 value is 10.4 mg/kg (88JMC1786). 

An overexpression of Gia-2 and Gia-3 proteins as well as their genes was shown in hearts and aorta from spontaneously hypertensive rats (SHRs), deoxycorticosterone acetate (DOCA)-salt hypertensive rats (HR), Atu-nitro-L-arginine methylester (L-NAME) HR, and 1 kidney 1 clip (1K1C) HR (Anand-Srivastava et al. 1991, 1993 Bohm et al. 1992, 1993 Thibault and Anand-Srivastava 1992 Anand-Srivastava 1993 DiFusco and Anand-Srivastava 1997, 2000 Ge et al. 1999, 2006), whereas Gsa protein and its gene were not altered in SHRs, 1K1C and L-NAME HR, and were decreased in DOCA-salt HRs (Anand-Srivastava et al. 1991 Anand-Srivastava 1992, 1993 Thibault and Anand-Srivastava 1992 DiFusco and Anand-Srivastava 1997, 2000 Ge et al. 1999, 2006). In addition, the levels of Goa in heart were not altered (Anand-Srivastava 1992). Alterations in Gi-protein levels have been shown to be reflected in altered responsiveness of adenylyl cyclase to stimulatory and inhibitory hormones in SHRs, and experimental models of hypertensive rats (Anand-Srivastava et al. 1991 Anand-Srivastava 1992). However,... 

Fig. 1.1 Effect of in vivo pertussis toxin (PT) treatment on the development of blood pressure in spontaneously hypertensive rats (SHR) Two-week-old SHR and WKY were injected intraperi-toneally with PT (1.5 pg/lOOg body weight) in 0.01M sodium phosphate buffer, pH 7.0, containing 0.05 M NaCl (PT-treated) or vehicle (control WKY and control SHR), as described earlier (Li and Anand-Srivastava 2002) A second injection of PT (1.5 pg/100g body weight) was given at 6 weeks to one group of PT-treated SHR and at 8 weeks to another group of PT-treated SHR and PT-treated WKY. Blood pressure was monitored weekly as described earlier (Li and Anand-Srivastava 2002). Values are means S.E.M. of five or six rats in each group. Reproduced with permission from Li and Anand-Srivastava (2002).

Zeng YY, Benishin CG, Pank PKT. 1991. Increased responsiveness of the adenylate cyclase (AC) signalling system in splenocyte membranes from spontaneously hypertensive rats (SHR) (abstract). FASEB J 5 A1597. 

Furthermore, the antihypertensive effect of whey proteins has been revealed in recent studies. Wu et al. (1998) showed that a diet supplemented with whey minerals had a clear antihypertensive effect. The development of hypertension was markedly attenuated and the systolic blood pressure (SBP) was about 50 mmHg lower in spontaneously hypertensive rats (SHR) receiving a diet supplemented with whey than in the control SHR group. Blood pressures in the normotensive Wistar-Kyoto rats remained comparable during the whole study. 

Caldum channel antagonist activity was determined in isolated rabbit ear artery rings depolarized by a high K+ concentration [7]. The duration of action in vitro (Dw) was determined by means of wash-out experiments. Rabbit ear artery rings were contracted by a submaximal concentration of calcium, and incubated with the tested compounds for 60 min. Subsequently, they were washed with saline solution until the initial contraction was restored. Dw was defined as the time required by the tissue to recover the basal effect elicited by a submaximal concentration of calcium [8], Antihypertensive activity and Dw were determined in chronically implanted spontaneously hypertensive rats (SHR) [9]. 

NO acts as a sympathoinhibitory substance within the central nervous system [44], Using SIN-1 (32), central NO administration has been shown to enhance acute hypoxic pulmonary vasoconstriction (HPV) [45], and accentuation of the HPV by NO is exacerbated in spontaneously hypertensive rats (SHR) compared with Wister-Kyoto (WKY) rats [46]. 

Further evidence that central 5-hydroxytryptamine (5-HT) neurones are involved in cardiovascular control systems is found in the observation that a central administration of the selective neurotoxin 5 6-dihydroxy-tryptamine causes a significant delay in the development of hypertension in young spontaneously hypertensive rats (SHRs).30 a further demonstration of the centrally-mediated hypotensive effect of methysergide has appeared 31 this may not be a result of 5-HT antagonism. 

A similar study of the anti-hypertensive activity of the alkaloids of Kopsia teoi were also carried out which were also prompted by positive results from preliminary screening of alkaloidal extracts. The major aspidofractinine alkaloid kopsingine (191) was found to produce dose-related decreases in mean arterial blood pressure and heart rate in anaesthetized spontaneously hypertensive rats (SHR) which were similar to those elicited in normotensive controls. The same depressor response was shown by the 12-demethoxy derivative (kopsaporine, 192) and the semisynthetic 14,15-dihydto derivative of kopsingine 252, indicating that minor modifications to the basic structure of kopsingine do not significantly alter... 

Very surprisingly, however, when the individual enantiomers 34-37 of meta and para trans-fluorobenzamides (see Table 2) were examined, it was found that the anticonvulsant activity resided predominantly in the 3i2,4S enantiomers 34 and 35. These compounds have the opposite stereochemistry to that of levcromakahm 2 and compound 35 did not significantly lower blood pressure at 10 mg/kg orally in the spontaneously hypertensive rat (SHR see figure 2). Thus it seems very unlikely that the anticonvulsant activity of 34 and 35 is a result of modulation of the t) e of channel with which levcromakalim 2 interacts. 

As early as in the 1970s, the potential use of cannabinoid ligands as antihypertensive agents had been considered (Archer 1974 Crawford and Merritt 1979 Varma et al. 1975 Zaugg and Kyncl 1983), in the hope that their neurobehavioral and cardiovascular effects could be separated. Although an early study in normotensive rats indicated rapidly developing tolerance to the hypotensive and bradycardic effects of THC (Adams et al. 1976), a subsequent study in spontaneously hypertensive rats (SHR) found no evidence for tolerance for the same effects during a similar, 10-day treatment period (Kosersky 1978). 

Tamashiro, H., M. Arakaki, H. Akagi, K. Hirayama, K. Mivao, and M.H. Smolensky. 1986a. Sex different of methylmercury toxicity in spontaneously hypertensive rats (SHR). Bull. EnvirorL Contain. Toxicol. 37(6) 916-924. 

Tamashiro et al. (1986) reported an increase in blood pressure in spontaneous hypertensive rats (SHR) exposed to MeHg at 2 mg/kg per day for 26 consecutive days. That effect was sex specific, being observed only in females. Considerable variation was observed in blood pressure for both the MeHg-exposed and the control rats. Differences were observed at only two time points, week 3 and week 5 of the study. 

Compounds 39, 78, and 79 showed a hypotensive effect in spontaneously hypertensive rat (SHR) [80,107,108], Compound 43 showed an antihypertensive effect in deoxycorticosterone acetate (DOCA)-salt hypertensive rat. In this model, a diet containing 43 markedly suppressed the increase of blood pressure [109]. Compound 43 showed a weak inhibitory activity on angiotensin converting enzyme (ACE) [110]. Graminone B (151) inhibited the contractile response of rabbit isolated aorta [111]. 

Miller, D.W. Tessel, R. (1991) Age-dependent hyperresponsiveness of spontaneously hypertensive rats (SHR) to the pressor effects of intravenous neuropeptide Y (NPY) The role of mode of peptide administration and plasma NPY-like immunoreactivity. J. Cardiovasc. Pharmacol. 18, 647-656. 

---